Abstract: Decades of experimentation with a variety of pharmacological treatments have identified... more Abstract: Decades of experimentation with a variety of pharmacological treatments have identified some effective therapies for heroin addiction but not for cocaine addiction. This may be due, at least in part, to our incomplete understanding of the factors involved in the differential vulnerability to these addictions, which are often considered mere variations of the same disorder. Indeed, the preference for one drug or another has been variously attributed to factors such as drug availability or price, to the addict’s lifestyle, or even to chance. Yet, there is evidence of substance-specific influences on drug taking. Data from twin registries, for example, suggest that a sizeable portion of the variability in the susceptibility to drug abuse is due to environmental factors that are unique to opiates or to psychostimulants. Very little is known about the nature of these environmental influences. We report here original data, based on retrospective reports in human addicts, indicating that the setting of drug taking exerts a differential influence on heroin versus cocaine use. We also review additional clinical and pre-clinical data pointing to fundamental differences in the way in which the environment interacts with cocaine relative to heroin and other addictive drugs. These findings - as well as other evidence, including the lack of pharmacological treatments effective for both cocaine and heroin addiction - support the notion that much is to be gained by taking into account the substance-specific aspects of drug addiction. At a therapeutic level, for example, it appears reasonable to propose that cognitive-behavioral approaches should be tailored in a substance-specific manner in order to allow the addict to anticipate, and cope with, the risks associated to the various environmental settings of drug use.
Abstract
Rationale The circumstances of drug taking are thought to
play a role in drug abuse but ... more Abstract Rationale The circumstances of drug taking are thought to play a role in drug abuse but the evidence of it is anecdotal. Previous studies have shown that the intravenous selfadministration of cocaine is facilitated in rats non-residing in the test chambers relative to rats that live in the test chambers at all times. We investigated here whether environmental context could exert its modulatory influence on heroin and amphetamine self-administration as well. Materials and methods Independent groups of rats were given the possibility to self-administer different doses of heroin or amphetamine (12.5, 25.0, or 50.0 μg/kg). Some animals were housed in the self-administration chambers (resident groups) whereas other rats were transported to the self-administration chambers only for the test sessions (non-resident groups). Results Amphetamine-reinforcing effects were more pronounced in non-resident rats than in resident rats, as previously reported for cocaine. Quite unexpectedly, the opposite was found for heroin. Because of this surprising dissociation, some of the rats trained to self-administer amphetamine were later given the opportunity to selfadminister heroin. Also in this case, resident rats took more heroin than non-resident rats. Conclusions These findings suggest an unforeseen dissociation between opioid and psychostimulant reward and demonstrate that even in the laboratory rat some contexts are associated with the propensity to self-administer more opioid than psychostimulant drugs and vice versa, thus indicating that drug taking is influenced not only by economical or cultural factors but also can be modulated at a much more basic level by the setting in which drugs are experienced. Keywords Heroin . Amphetamine . Self-administration . Addiction . Drug abuse . Environment
Abstract
Rationale Previous studies have shown that environmental
context can powerfully modulate... more Abstract Rationale Previous studies have shown that environmental context can powerfully modulate the induction of psychomotor sensitization to cocaine in the rat. Rats that receive repeated administrations of cocaine in association with environmental novelty exhibit greater psychomotor sensitization than animals that receive the same treatments in their home cages. Objectives The goal of the present study was to investigate whether environmental context can exert its modulatory influence also on cocaine self-administration. Materials and methods Independent groups of rats with intravenous catheters were given the possibility to selfadminister different doses of cocaine (0.0, 0.2, 0.4, and 0.8 mg/kg per infusion) under two environmental conditions. Some animals were housed in the self-administration cages (home groups), whereas other rats were transported to the self-administration cages only for the test sessions (novelty groups). Results Environmental “novelty” facilitated the acquisition of cocaine self-administration at the doses of 0.2 and 0.4 mg/kg per infusion. When rats were given access to a higher dose of cocaine (0.8 mg/kg per infusion), there were no significant group differences in drug taking. Environmental context had no effect on the self-administration of the vehicle. Thus, it appears that environmental “novelty” produced a shift to the left in the dose-effect curve for cocaine self-administration. Furthermore, “novelty” enhanced the motivation of the rats to work for cocaine, as indicated by the results of a progressive ratio procedure. Conclusions The present findings demonstrate for the first time that the environment surrounding drug taking can alter both the intake of and motivation for cocaine.
Background: We have recently observed an unforeseen dissociation in the effect of environmental c... more Background: We have recently observed an unforeseen dissociation in the effect of environmental context on heroin versus cocaine self-administration in rats. Rats housed in the self-administration chambers (Residents) took more heroin than rats that were transferred to the self-administration chambers only for the test sessions (Nonresidents). The contrary was found for cocaine. The twofold aim of the present study was to investigate: 1) drug choice as a function of ambience in rats given access to both cocaine and heroin, and 2) ambience of choice for cocaine- versus heroin-taking in human addicts. Methods: Resident and Nonresident rats with double-lumen intrajugular catheters were trained to self-administer cocaine (400 g/kg/ infusion) and heroin (25 g/kg/infusion) on alternate days and then given the opportunity to choose between the two drugs during seven daily sessions. In the human study, we asked heroin and cocaine abusers where they preferred to take these drugs. Results: Approximately 46.7% of Resident rats exhibited a preference for heroin over cocaine; 33.3% preferred cocaine, and 20% expressed no preference. In contrast, only 8.3% of Nonresident rats preferred heroin, whereas 66.7% preferred cocaine, and 25% expressed no preference. In the human study, 73% of co-abusers reported that they used heroin exclusively or mostly at home (22% used it outside the home), whereas only 25% reported using cocaine at home (67% took it outside their homes). Conclusions: Environmental context plays an important role in drug choice in both humans and rats self-administering heroin and cocaine.
The effect of a systemic (IP) treatment with 1.0, 3.0 and 9.0 mg/kg U-50,488H (U50), a highly sel... more The effect of a systemic (IP) treatment with 1.0, 3.0 and 9.0 mg/kg U-50,488H (U50), a highly selective kappa-agonist, on spontaneous, nocturnal ingestive behavior of the rat was studied using a microcomputer controlled data acquisition system. The latency to initiate drinking was increased and drinking behavior was suppressed in the first hour after injection in a dose-dependent manner. The consummatory indices of drinking were not affected. After this period of adipsia, a phase of polydipsia, that was probably due to the diuretic effect of U50, was evident. The prophagic effect of U50 was evident only at the dose of 3 mg/kg and was accompanied by an increased duration of feeding episodes but not by a reduced latency to feed. These results suggest that kappa-receptors play a pivotal role in modulating spontaneous drinking in the normally hydrated rat and that this control is mainly exerted on the motivational aspect of drinking.
Rationale We have previously shown that environmental novelty can potentiate the activating effec... more Rationale We have previously shown that environmental novelty can potentiate the activating effects of morphine and the development of sensitization to this effect. Objectives Our main goal was to determine whether environmental novelty can also modulate the prophagic (time spent eating and food intake; experiment 1) and/or the analgesic (tail-flick test; experiments 2 and 3) effect of morphine, as well as the development of tolerance or sensitization to these effects. Methods In experiment 1, two groups of rats were administered seven intraperitoneal (i.p.) injections of either saline or morphine (4.0 mg/kg) either in their home cages (home groups) or in a distinct environment (novelty groups). After 7 days of withdrawal, both groups underwent a morphine challenge (4.0 mg/kg, i.p.). In experiment 2, home and novelty rats were administered four doses of morphine (0.0, 2.0, 4.0, and 8.0 mg/kg, i.p.) following a counterbalanced order. In experiment 3, home and novelty rats were administered eight intraperitoneal (i.p.) injections of either saline or morphine (8.0 mg/kg) and then given a morphine challenge (4.0 mg/kg). Results Environmental novelty enhanced the locomotor activating effect of morphine and the expression of sensitization to this effect (even after a period of withdrawal). Environmental novelty had relatively little effect on morphine-induced eating, and no effect on morphine-induced analgesia. Conclusions Environmental context can have very different consequences on distinct drug effects as well as on distinct neurobehavioral adaptations to the same drug treatment (e.g., psychomotor sensitization versus analgesic tolerance).
The acute psychomotor response and development of sensitization to amphetamine is attenuated if ... more The acute psychomotor response and development of sensitization to amphetamine is attenuated if IP injections are given in the cage where a rat lives relative to when injections are given in a novel but physically identical test environment. Furthermore, when the environmental cues predicting IP injections are completely eliminated by using remotely activated IV injections in the home cage, 1.0 mg/kg amphetamine produces a very small acute response and no sensitization. The same treatments do produce sensitization if IV injections are signaled by placement of the rat in a novel test cage. The present experiment was designed to determine if there is a similar effect of environmental condition on the response to IV cocaine, and to what extent the effect may be dose-dependent. This was accomplished by comparing the psychomotor activating effects (rotational behavior) of repeated IV administrations of one of eight doses of cocaine (0.0, 0.3, 0.6, 1.2, 2.4, 3.6, 4.8, or 7.2 mg/kg) given in the home cage, with infusions of the same doses given in a novel test cage. There was no effect of environment on the acute psychomotor response to cocaine. There was, however, a significant effect of environment on the induction of sensitization. A higher dose of cocaine was required to induce sensitization when IV administrations were given in the home cage than when they were given in a physically identical but novel test environment. At high doses, however, cocaine induced sensitization regardless of environmental condition. The results suggest that the effect of this environmental manipulation is to shift the dose-effect curve for the induction of sensitization, and support the notion that the ability of psychostimulant drugs to induce sensitization can be modulated by the circumstances surrounding drug administration.
Rationale: We have previously shown that environmental novelty enhances the behavioral activating... more Rationale: We have previously shown that environmental novelty enhances the behavioral activating effects of amphetamine and amphetamine-induced expression of the immediate early gene c-fos in the striatal complex, particularly in the most caudal portion of the caudate. In contrast, we found no effect of novelty on the ability of amphetamine to induce dopamine (DA) overflow in the rostral caudate or in the core of the nucleus accumbens. Objectives: The twofold aim of the present study was to determine the effect of environmental novelty on (1) amphetamine-induced DA overflow in the shell of the nucleus accumbens and in the caudal portions of the caudate, and (2) glutamate and aspartate overflow in the caudal portions of the caudate. Methods: Two groups of rats with a unilateral 6-hydroxydopamine lesion of the mesostriatal dopaminergic system received amphetamine (0.5 mg/kg, i.v.) in physically identical cages. For one group, the cages were also the home environment, whereas, for the other group, they were a completely novel environment. In vivo microdialysis was used to estimate DA, glutamate, and aspartate concentrations. Results: Environmental novelty enhanced amphetamine-induced rotational behavior (experiments 1–3) but did not alter amphetamine-induced DA overflow in either the shell of the nucleus accumbens (experiment 1) or the caudate (experiment 2). In addition, the ability of environmental novelty to enhance amphetamine-induced behavioral activation was not associated with changes in glutamate or aspartate efflux in the caudate (experiment 3). Conclusions: The present data indicate that the psychomotor activating effects of amphetamine can be modulated by environmental context independent of its primary neuropharmacological actions in the striatal complex.
Abstract: Decades of experimentation with a variety of pharmacological treatments have identified... more Abstract: Decades of experimentation with a variety of pharmacological treatments have identified some effective therapies for heroin addiction but not for cocaine addiction. This may be due, at least in part, to our incomplete understanding of the factors involved in the differential vulnerability to these addictions, which are often considered mere variations of the same disorder. Indeed, the preference for one drug or another has been variously attributed to factors such as drug availability or price, to the addict’s lifestyle, or even to chance. Yet, there is evidence of substance-specific influences on drug taking. Data from twin registries, for example, suggest that a sizeable portion of the variability in the susceptibility to drug abuse is due to environmental factors that are unique to opiates or to psychostimulants. Very little is known about the nature of these environmental influences. We report here original data, based on retrospective reports in human addicts, indicating that the setting of drug taking exerts a differential influence on heroin versus cocaine use. We also review additional clinical and pre-clinical data pointing to fundamental differences in the way in which the environment interacts with cocaine relative to heroin and other addictive drugs. These findings - as well as other evidence, including the lack of pharmacological treatments effective for both cocaine and heroin addiction - support the notion that much is to be gained by taking into account the substance-specific aspects of drug addiction. At a therapeutic level, for example, it appears reasonable to propose that cognitive-behavioral approaches should be tailored in a substance-specific manner in order to allow the addict to anticipate, and cope with, the risks associated to the various environmental settings of drug use.
Abstract
Rationale The circumstances of drug taking are thought to
play a role in drug abuse but ... more Abstract Rationale The circumstances of drug taking are thought to play a role in drug abuse but the evidence of it is anecdotal. Previous studies have shown that the intravenous selfadministration of cocaine is facilitated in rats non-residing in the test chambers relative to rats that live in the test chambers at all times. We investigated here whether environmental context could exert its modulatory influence on heroin and amphetamine self-administration as well. Materials and methods Independent groups of rats were given the possibility to self-administer different doses of heroin or amphetamine (12.5, 25.0, or 50.0 μg/kg). Some animals were housed in the self-administration chambers (resident groups) whereas other rats were transported to the self-administration chambers only for the test sessions (non-resident groups). Results Amphetamine-reinforcing effects were more pronounced in non-resident rats than in resident rats, as previously reported for cocaine. Quite unexpectedly, the opposite was found for heroin. Because of this surprising dissociation, some of the rats trained to self-administer amphetamine were later given the opportunity to selfadminister heroin. Also in this case, resident rats took more heroin than non-resident rats. Conclusions These findings suggest an unforeseen dissociation between opioid and psychostimulant reward and demonstrate that even in the laboratory rat some contexts are associated with the propensity to self-administer more opioid than psychostimulant drugs and vice versa, thus indicating that drug taking is influenced not only by economical or cultural factors but also can be modulated at a much more basic level by the setting in which drugs are experienced. Keywords Heroin . Amphetamine . Self-administration . Addiction . Drug abuse . Environment
Abstract
Rationale Previous studies have shown that environmental
context can powerfully modulate... more Abstract Rationale Previous studies have shown that environmental context can powerfully modulate the induction of psychomotor sensitization to cocaine in the rat. Rats that receive repeated administrations of cocaine in association with environmental novelty exhibit greater psychomotor sensitization than animals that receive the same treatments in their home cages. Objectives The goal of the present study was to investigate whether environmental context can exert its modulatory influence also on cocaine self-administration. Materials and methods Independent groups of rats with intravenous catheters were given the possibility to selfadminister different doses of cocaine (0.0, 0.2, 0.4, and 0.8 mg/kg per infusion) under two environmental conditions. Some animals were housed in the self-administration cages (home groups), whereas other rats were transported to the self-administration cages only for the test sessions (novelty groups). Results Environmental “novelty” facilitated the acquisition of cocaine self-administration at the doses of 0.2 and 0.4 mg/kg per infusion. When rats were given access to a higher dose of cocaine (0.8 mg/kg per infusion), there were no significant group differences in drug taking. Environmental context had no effect on the self-administration of the vehicle. Thus, it appears that environmental “novelty” produced a shift to the left in the dose-effect curve for cocaine self-administration. Furthermore, “novelty” enhanced the motivation of the rats to work for cocaine, as indicated by the results of a progressive ratio procedure. Conclusions The present findings demonstrate for the first time that the environment surrounding drug taking can alter both the intake of and motivation for cocaine.
Background: We have recently observed an unforeseen dissociation in the effect of environmental c... more Background: We have recently observed an unforeseen dissociation in the effect of environmental context on heroin versus cocaine self-administration in rats. Rats housed in the self-administration chambers (Residents) took more heroin than rats that were transferred to the self-administration chambers only for the test sessions (Nonresidents). The contrary was found for cocaine. The twofold aim of the present study was to investigate: 1) drug choice as a function of ambience in rats given access to both cocaine and heroin, and 2) ambience of choice for cocaine- versus heroin-taking in human addicts. Methods: Resident and Nonresident rats with double-lumen intrajugular catheters were trained to self-administer cocaine (400 g/kg/ infusion) and heroin (25 g/kg/infusion) on alternate days and then given the opportunity to choose between the two drugs during seven daily sessions. In the human study, we asked heroin and cocaine abusers where they preferred to take these drugs. Results: Approximately 46.7% of Resident rats exhibited a preference for heroin over cocaine; 33.3% preferred cocaine, and 20% expressed no preference. In contrast, only 8.3% of Nonresident rats preferred heroin, whereas 66.7% preferred cocaine, and 25% expressed no preference. In the human study, 73% of co-abusers reported that they used heroin exclusively or mostly at home (22% used it outside the home), whereas only 25% reported using cocaine at home (67% took it outside their homes). Conclusions: Environmental context plays an important role in drug choice in both humans and rats self-administering heroin and cocaine.
The effect of a systemic (IP) treatment with 1.0, 3.0 and 9.0 mg/kg U-50,488H (U50), a highly sel... more The effect of a systemic (IP) treatment with 1.0, 3.0 and 9.0 mg/kg U-50,488H (U50), a highly selective kappa-agonist, on spontaneous, nocturnal ingestive behavior of the rat was studied using a microcomputer controlled data acquisition system. The latency to initiate drinking was increased and drinking behavior was suppressed in the first hour after injection in a dose-dependent manner. The consummatory indices of drinking were not affected. After this period of adipsia, a phase of polydipsia, that was probably due to the diuretic effect of U50, was evident. The prophagic effect of U50 was evident only at the dose of 3 mg/kg and was accompanied by an increased duration of feeding episodes but not by a reduced latency to feed. These results suggest that kappa-receptors play a pivotal role in modulating spontaneous drinking in the normally hydrated rat and that this control is mainly exerted on the motivational aspect of drinking.
Rationale We have previously shown that environmental novelty can potentiate the activating effec... more Rationale We have previously shown that environmental novelty can potentiate the activating effects of morphine and the development of sensitization to this effect. Objectives Our main goal was to determine whether environmental novelty can also modulate the prophagic (time spent eating and food intake; experiment 1) and/or the analgesic (tail-flick test; experiments 2 and 3) effect of morphine, as well as the development of tolerance or sensitization to these effects. Methods In experiment 1, two groups of rats were administered seven intraperitoneal (i.p.) injections of either saline or morphine (4.0 mg/kg) either in their home cages (home groups) or in a distinct environment (novelty groups). After 7 days of withdrawal, both groups underwent a morphine challenge (4.0 mg/kg, i.p.). In experiment 2, home and novelty rats were administered four doses of morphine (0.0, 2.0, 4.0, and 8.0 mg/kg, i.p.) following a counterbalanced order. In experiment 3, home and novelty rats were administered eight intraperitoneal (i.p.) injections of either saline or morphine (8.0 mg/kg) and then given a morphine challenge (4.0 mg/kg). Results Environmental novelty enhanced the locomotor activating effect of morphine and the expression of sensitization to this effect (even after a period of withdrawal). Environmental novelty had relatively little effect on morphine-induced eating, and no effect on morphine-induced analgesia. Conclusions Environmental context can have very different consequences on distinct drug effects as well as on distinct neurobehavioral adaptations to the same drug treatment (e.g., psychomotor sensitization versus analgesic tolerance).
The acute psychomotor response and development of sensitization to amphetamine is attenuated if ... more The acute psychomotor response and development of sensitization to amphetamine is attenuated if IP injections are given in the cage where a rat lives relative to when injections are given in a novel but physically identical test environment. Furthermore, when the environmental cues predicting IP injections are completely eliminated by using remotely activated IV injections in the home cage, 1.0 mg/kg amphetamine produces a very small acute response and no sensitization. The same treatments do produce sensitization if IV injections are signaled by placement of the rat in a novel test cage. The present experiment was designed to determine if there is a similar effect of environmental condition on the response to IV cocaine, and to what extent the effect may be dose-dependent. This was accomplished by comparing the psychomotor activating effects (rotational behavior) of repeated IV administrations of one of eight doses of cocaine (0.0, 0.3, 0.6, 1.2, 2.4, 3.6, 4.8, or 7.2 mg/kg) given in the home cage, with infusions of the same doses given in a novel test cage. There was no effect of environment on the acute psychomotor response to cocaine. There was, however, a significant effect of environment on the induction of sensitization. A higher dose of cocaine was required to induce sensitization when IV administrations were given in the home cage than when they were given in a physically identical but novel test environment. At high doses, however, cocaine induced sensitization regardless of environmental condition. The results suggest that the effect of this environmental manipulation is to shift the dose-effect curve for the induction of sensitization, and support the notion that the ability of psychostimulant drugs to induce sensitization can be modulated by the circumstances surrounding drug administration.
Rationale: We have previously shown that environmental novelty enhances the behavioral activating... more Rationale: We have previously shown that environmental novelty enhances the behavioral activating effects of amphetamine and amphetamine-induced expression of the immediate early gene c-fos in the striatal complex, particularly in the most caudal portion of the caudate. In contrast, we found no effect of novelty on the ability of amphetamine to induce dopamine (DA) overflow in the rostral caudate or in the core of the nucleus accumbens. Objectives: The twofold aim of the present study was to determine the effect of environmental novelty on (1) amphetamine-induced DA overflow in the shell of the nucleus accumbens and in the caudal portions of the caudate, and (2) glutamate and aspartate overflow in the caudal portions of the caudate. Methods: Two groups of rats with a unilateral 6-hydroxydopamine lesion of the mesostriatal dopaminergic system received amphetamine (0.5 mg/kg, i.v.) in physically identical cages. For one group, the cages were also the home environment, whereas, for the other group, they were a completely novel environment. In vivo microdialysis was used to estimate DA, glutamate, and aspartate concentrations. Results: Environmental novelty enhanced amphetamine-induced rotational behavior (experiments 1–3) but did not alter amphetamine-induced DA overflow in either the shell of the nucleus accumbens (experiment 1) or the caudate (experiment 2). In addition, the ability of environmental novelty to enhance amphetamine-induced behavioral activation was not associated with changes in glutamate or aspartate efflux in the caudate (experiment 3). Conclusions: The present data indicate that the psychomotor activating effects of amphetamine can be modulated by environmental context independent of its primary neuropharmacological actions in the striatal complex.
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Papers by Aldo Badiani
one drug or another has been variously attributed to factors such as drug availability or price, to the addict’s lifestyle, or even to chance. Yet, there is evidence of substance-specific influences on drug taking. Data from twin registries, for example, suggest that a sizeable portion of the variability in the susceptibility to drug abuse is due to environmental factors that are unique to opiates or to psychostimulants. Very little is known about the nature of these environmental influences. We report here original data, based on retrospective reports in human addicts, indicating that the setting of drug taking exerts a differential influence on heroin versus cocaine use. We also review additional clinical and pre-clinical data pointing to fundamental differences in the way in which the environment interacts with cocaine relative to heroin and other addictive drugs. These findings - as well as other evidence, including the lack of pharmacological treatments effective for both cocaine and heroin addiction - support the notion that much is to be gained by taking into account the substance-specific aspects of drug addiction. At a therapeutic level, for example, it appears reasonable to propose that cognitive-behavioral approaches should be tailored in a substance-specific manner in order to allow the addict to anticipate, and cope with, the risks associated to the various environmental settings of drug use.
Rationale The circumstances of drug taking are thought to
play a role in drug abuse but the evidence of it is anecdotal.
Previous studies have shown that the intravenous selfadministration
of cocaine is facilitated in rats non-residing
in the test chambers relative to rats that live in the test
chambers at all times. We investigated here whether
environmental context could exert its modulatory influence
on heroin and amphetamine self-administration as well.
Materials and methods Independent groups of rats were
given the possibility to self-administer different doses of
heroin or amphetamine (12.5, 25.0, or 50.0 μg/kg). Some
animals were housed in the self-administration chambers
(resident groups) whereas other rats were transported to the
self-administration chambers only for the test sessions
(non-resident groups).
Results Amphetamine-reinforcing effects were more pronounced
in non-resident rats than in resident rats, as
previously reported for cocaine. Quite unexpectedly, the
opposite was found for heroin. Because of this surprising
dissociation, some of the rats trained to self-administer
amphetamine were later given the opportunity to selfadminister
heroin. Also in this case, resident rats took more
heroin than non-resident rats.
Conclusions These findings suggest an unforeseen dissociation
between opioid and psychostimulant reward and
demonstrate that even in the laboratory rat some contexts
are associated with the propensity to self-administer more
opioid than psychostimulant drugs and vice versa, thus
indicating that drug taking is influenced not only by
economical or cultural factors but also can be modulated
at a much more basic level by the setting in which drugs are
experienced.
Keywords Heroin . Amphetamine . Self-administration .
Addiction . Drug abuse . Environment
Rationale Previous studies have shown that environmental
context can powerfully modulate the induction of psychomotor
sensitization to cocaine in the rat. Rats that receive
repeated administrations of cocaine in association with
environmental novelty exhibit greater psychomotor sensitization
than animals that receive the same treatments in their
home cages.
Objectives The goal of the present study was to investigate
whether environmental context can exert its modulatory
influence also on cocaine self-administration.
Materials and methods Independent groups of rats with
intravenous catheters were given the possibility to selfadminister
different doses of cocaine (0.0, 0.2, 0.4, and
0.8 mg/kg per infusion) under two environmental conditions.
Some animals were housed in the self-administration
cages (home groups), whereas other rats were transported to
the self-administration cages only for the test sessions
(novelty groups).
Results Environmental “novelty” facilitated the acquisition
of cocaine self-administration at the doses of 0.2 and
0.4 mg/kg per infusion. When rats were given access to a
higher dose of cocaine (0.8 mg/kg per infusion), there
were no significant group differences in drug taking.
Environmental context had no effect on the self-administration
of the vehicle. Thus, it appears that environmental
“novelty” produced a shift to the left in the dose-effect
curve for cocaine self-administration. Furthermore, “novelty”
enhanced the motivation of the rats to work for
cocaine, as indicated by the results of a progressive ratio
procedure.
Conclusions The present findings demonstrate for the first
time that the environment surrounding drug taking can alter
both the intake of and motivation for cocaine.
self-administration in rats. Rats housed in the self-administration chambers (Residents) took more heroin than rats that were transferred to
the self-administration chambers only for the test sessions (Nonresidents). The contrary was found for cocaine. The twofold aim of the
present study was to investigate: 1) drug choice as a function of ambience in rats given access to both cocaine and heroin, and 2) ambience
of choice for cocaine- versus heroin-taking in human addicts.
Methods: Resident and Nonresident rats with double-lumen intrajugular catheters were trained to self-administer cocaine (400 g/kg/
infusion) and heroin (25 g/kg/infusion) on alternate days and then given the opportunity to choose between the two drugs during seven
daily sessions. In the human study, we asked heroin and cocaine abusers where they preferred to take these drugs.
Results: Approximately 46.7% of Resident rats exhibited a preference for heroin over cocaine; 33.3% preferred cocaine, and 20% expressed
no preference. In contrast, only 8.3% of Nonresident rats preferred heroin, whereas 66.7% preferred cocaine, and 25% expressed no
preference. In the human study, 73% of co-abusers reported that they used heroin exclusively or mostly at home (22% used it outside the
home), whereas only 25% reported using cocaine at home (67% took it outside their homes).
Conclusions: Environmental context plays an important role in drug choice in both humans and rats self-administering heroin and cocaine.
one drug or another has been variously attributed to factors such as drug availability or price, to the addict’s lifestyle, or even to chance. Yet, there is evidence of substance-specific influences on drug taking. Data from twin registries, for example, suggest that a sizeable portion of the variability in the susceptibility to drug abuse is due to environmental factors that are unique to opiates or to psychostimulants. Very little is known about the nature of these environmental influences. We report here original data, based on retrospective reports in human addicts, indicating that the setting of drug taking exerts a differential influence on heroin versus cocaine use. We also review additional clinical and pre-clinical data pointing to fundamental differences in the way in which the environment interacts with cocaine relative to heroin and other addictive drugs. These findings - as well as other evidence, including the lack of pharmacological treatments effective for both cocaine and heroin addiction - support the notion that much is to be gained by taking into account the substance-specific aspects of drug addiction. At a therapeutic level, for example, it appears reasonable to propose that cognitive-behavioral approaches should be tailored in a substance-specific manner in order to allow the addict to anticipate, and cope with, the risks associated to the various environmental settings of drug use.
Rationale The circumstances of drug taking are thought to
play a role in drug abuse but the evidence of it is anecdotal.
Previous studies have shown that the intravenous selfadministration
of cocaine is facilitated in rats non-residing
in the test chambers relative to rats that live in the test
chambers at all times. We investigated here whether
environmental context could exert its modulatory influence
on heroin and amphetamine self-administration as well.
Materials and methods Independent groups of rats were
given the possibility to self-administer different doses of
heroin or amphetamine (12.5, 25.0, or 50.0 μg/kg). Some
animals were housed in the self-administration chambers
(resident groups) whereas other rats were transported to the
self-administration chambers only for the test sessions
(non-resident groups).
Results Amphetamine-reinforcing effects were more pronounced
in non-resident rats than in resident rats, as
previously reported for cocaine. Quite unexpectedly, the
opposite was found for heroin. Because of this surprising
dissociation, some of the rats trained to self-administer
amphetamine were later given the opportunity to selfadminister
heroin. Also in this case, resident rats took more
heroin than non-resident rats.
Conclusions These findings suggest an unforeseen dissociation
between opioid and psychostimulant reward and
demonstrate that even in the laboratory rat some contexts
are associated with the propensity to self-administer more
opioid than psychostimulant drugs and vice versa, thus
indicating that drug taking is influenced not only by
economical or cultural factors but also can be modulated
at a much more basic level by the setting in which drugs are
experienced.
Keywords Heroin . Amphetamine . Self-administration .
Addiction . Drug abuse . Environment
Rationale Previous studies have shown that environmental
context can powerfully modulate the induction of psychomotor
sensitization to cocaine in the rat. Rats that receive
repeated administrations of cocaine in association with
environmental novelty exhibit greater psychomotor sensitization
than animals that receive the same treatments in their
home cages.
Objectives The goal of the present study was to investigate
whether environmental context can exert its modulatory
influence also on cocaine self-administration.
Materials and methods Independent groups of rats with
intravenous catheters were given the possibility to selfadminister
different doses of cocaine (0.0, 0.2, 0.4, and
0.8 mg/kg per infusion) under two environmental conditions.
Some animals were housed in the self-administration
cages (home groups), whereas other rats were transported to
the self-administration cages only for the test sessions
(novelty groups).
Results Environmental “novelty” facilitated the acquisition
of cocaine self-administration at the doses of 0.2 and
0.4 mg/kg per infusion. When rats were given access to a
higher dose of cocaine (0.8 mg/kg per infusion), there
were no significant group differences in drug taking.
Environmental context had no effect on the self-administration
of the vehicle. Thus, it appears that environmental
“novelty” produced a shift to the left in the dose-effect
curve for cocaine self-administration. Furthermore, “novelty”
enhanced the motivation of the rats to work for
cocaine, as indicated by the results of a progressive ratio
procedure.
Conclusions The present findings demonstrate for the first
time that the environment surrounding drug taking can alter
both the intake of and motivation for cocaine.
self-administration in rats. Rats housed in the self-administration chambers (Residents) took more heroin than rats that were transferred to
the self-administration chambers only for the test sessions (Nonresidents). The contrary was found for cocaine. The twofold aim of the
present study was to investigate: 1) drug choice as a function of ambience in rats given access to both cocaine and heroin, and 2) ambience
of choice for cocaine- versus heroin-taking in human addicts.
Methods: Resident and Nonresident rats with double-lumen intrajugular catheters were trained to self-administer cocaine (400 g/kg/
infusion) and heroin (25 g/kg/infusion) on alternate days and then given the opportunity to choose between the two drugs during seven
daily sessions. In the human study, we asked heroin and cocaine abusers where they preferred to take these drugs.
Results: Approximately 46.7% of Resident rats exhibited a preference for heroin over cocaine; 33.3% preferred cocaine, and 20% expressed
no preference. In contrast, only 8.3% of Nonresident rats preferred heroin, whereas 66.7% preferred cocaine, and 25% expressed no
preference. In the human study, 73% of co-abusers reported that they used heroin exclusively or mostly at home (22% used it outside the
home), whereas only 25% reported using cocaine at home (67% took it outside their homes).
Conclusions: Environmental context plays an important role in drug choice in both humans and rats self-administering heroin and cocaine.