Anxiolytics that act as GABA A agonists and those that act as 5-HT 1A receptor agonists all reduc... more Anxiolytics that act as GABA A agonists and those that act as 5-HT 1A receptor agonists all reduce the frequency of hippocampal rhythmic slow activity (RSA). Changes in RSA have been linked to changes in behavioural inhibition and therefore anxiety – but this has not been tested with specific serotonin reuptake inhibitors, which are antidepressant and anxiolytic; therefore we tested the effects of fluoxetine on RSA and behavioural inhibition. Fluoxetine (FLU; 10 and 20 mg/kg, intraperitoneally) produced a dose-related reduction in the frequency of reticular-elicited RSA. Groups of rats received, intraperitoneally, either (i) saline, or 5 mg/kg fluoxetine, or 10 mg/kg fluoxetine; or (ii) saline, or 20 mg/kg fluoxetine, or 6.6 mg/kg of the 5-HT 1A agonist buspirone (BUS) and were tested on a fixed interval 60-s schedule and a differential reinforcement of low rates 15-s schedule. FLU at 5 mg/kg produced effects similar to low doses of BUS and other anxiolytics. FLU (10 and 20 mg/kg) produced effects more like those reported earlier for higher doses of BUS. These results continue to link anxiolysis, RSA and behavioural inhibition, and suggest that serotonergic anxiolytics share some of the central actions of GABAergic anxiolytics, but at higher doses, administered acutely, have distinct side effects that can obscure their anxiolytic action in behavioural tasks.
Nebraska Symposium on Motivation. Nebraska Symposium on Motivation, 1996
... Gray's (1982a) book lay firmly in the psychological tradition, defining (p. 426) anxiety... more ... Gray's (1982a) book lay firmly in the psychological tradition, defining (p. 426) anxiety symp-toms as" those that are found in individuals whose personality lies in the neurotic introvert portion of the multidimensional personality space described by Eysenck and Eysenck (1969 ...
The Quarterly journal of experimental psychology, 1979
Three experiments are reported testing two alternative hypotheses concerning the behavioural effe... more Three experiments are reported testing two alternative hypotheses concerning the behavioural effects of sodium amylobarbitone (SA): (1) that it blocks the after-effect of nonreward; (2) that it blocks conditioned frustration, elicited by stimuli associated with nonreward. In support of (2) Experiment I showed that SA given in acquisition abolished the partial reinforcement extinction effect (PREE) when rats were run at one trial a day in an alley for food reward on a continuous (CRF) or partial (PRF) reinforcement schedule. Experiment II showed that, in the goal section, the effect of the drug on the PREE was due to its presence during acquisition and was not due to state dependency; but the effect of the drug in the start section was consistent with state dependency of the PREE. In Experiment III, in opposition to (1) and again in support of (2), SA given to rats trained to show patterned running for water reward on a single alternation schedule blocked patterning by increasing running speeds on nonreward trials, not by decreasing running speeds on rewarded trials.
The literature on the behavioural effects of septal and hippocampal lesions is classified accordi... more The literature on the behavioural effects of septal and hippocampal lesions is classified according to behavioural paradigm. The effects of the two kinds of lesion are summarized and compared to each other. A 'septo-hippocampal syndrome,' consisting of the effects common to both lesions, is delineated, and divergences between the effects of the two lesions are noted.
The effects of buspirone were tested on rearing in an open field. Six different doses of buspiron... more The effects of buspirone were tested on rearing in an open field. Six different doses of buspirone (10, 3.3, 1.1, 0.3, 0.1 and 0.04 mg/kg) and a single dose of chlordiazepoxide (5 mg/kg) were administered i.p. to separate groups of rats. Buspirone produced a dose-dependent decrease in rearing in the range 0.04-10 mg/kg, whereas only the higher doses (10 and 3.3 mg/kg) decreased ambulation significantly. Chlordiazepoxide reduced rearing to an extent equivalent to 1 mg/kg of buspirone. Together with data in the literature, the results suggest that 5-HT1A agonists affect rearing at lower doses than ambulation; that the effects of buspirone in the open field are similar to classical anxiolytics; and that changes in rearing may be more closely related to anxiolytic than muscle relaxant, anti-convulsant and other GABA-mediated effects of the classical anxiolytics.
The ability of the opiate antagonist, naloxone, to block the anti-conflict effects of the benzodi... more The ability of the opiate antagonist, naloxone, to block the anti-conflict effects of the benzodiazepines suggests endogenous opioid involvement in the mechanism of action of these drugs. However naloxone's ability to attenuate the effects of the benzodiazepines in animal conflict paradigms appears to be schedule specific. It is effective in acquisition of a differential reinforcement of low rates of response (DRL) schedule but not in acquisition of a non-reward successive discrimination schedule. We tested the effects of naloxone and chlordiazepoxide on acquisition of DRL and on acquisition of a version of the same schedule (signalled DRL) which was like successive discrimination in having an explicit visual signal of non-reward. Chlordiazepoxide (5 mg/kg i.p.) impaired DRL responding by increasing burst responding and premature responding close to the criterion interval. Naloxone (3 mg/kg i.p.) alone decreased burst and premature responding, it also blocked the effects of chlordiazepoxide. The signalled DRL schedule produced essentially similar drug effects. Clearly the critical schedule parameter determining whether naloxone will attenuate the anxiolytic actions of the benzodiazepines is not the presence or absence of an explicit signal of conflict.
Anxiolytics that act as GABA A agonists and those that act as 5-HT 1A receptor agonists all reduc... more Anxiolytics that act as GABA A agonists and those that act as 5-HT 1A receptor agonists all reduce the frequency of hippocampal rhythmic slow activity (RSA). Changes in RSA have been linked to changes in behavioural inhibition and therefore anxiety – but this has not been tested with specific serotonin reuptake inhibitors, which are antidepressant and anxiolytic; therefore we tested the effects of fluoxetine on RSA and behavioural inhibition. Fluoxetine (FLU; 10 and 20 mg/kg, intraperitoneally) produced a dose-related reduction in the frequency of reticular-elicited RSA. Groups of rats received, intraperitoneally, either (i) saline, or 5 mg/kg fluoxetine, or 10 mg/kg fluoxetine; or (ii) saline, or 20 mg/kg fluoxetine, or 6.6 mg/kg of the 5-HT 1A agonist buspirone (BUS) and were tested on a fixed interval 60-s schedule and a differential reinforcement of low rates 15-s schedule. FLU at 5 mg/kg produced effects similar to low doses of BUS and other anxiolytics. FLU (10 and 20 mg/kg) produced effects more like those reported earlier for higher doses of BUS. These results continue to link anxiolysis, RSA and behavioural inhibition, and suggest that serotonergic anxiolytics share some of the central actions of GABAergic anxiolytics, but at higher doses, administered acutely, have distinct side effects that can obscure their anxiolytic action in behavioural tasks.
Nebraska Symposium on Motivation. Nebraska Symposium on Motivation, 1996
... Gray's (1982a) book lay firmly in the psychological tradition, defining (p. 426) anxiety... more ... Gray's (1982a) book lay firmly in the psychological tradition, defining (p. 426) anxiety symp-toms as" those that are found in individuals whose personality lies in the neurotic introvert portion of the multidimensional personality space described by Eysenck and Eysenck (1969 ...
The Quarterly journal of experimental psychology, 1979
Three experiments are reported testing two alternative hypotheses concerning the behavioural effe... more Three experiments are reported testing two alternative hypotheses concerning the behavioural effects of sodium amylobarbitone (SA): (1) that it blocks the after-effect of nonreward; (2) that it blocks conditioned frustration, elicited by stimuli associated with nonreward. In support of (2) Experiment I showed that SA given in acquisition abolished the partial reinforcement extinction effect (PREE) when rats were run at one trial a day in an alley for food reward on a continuous (CRF) or partial (PRF) reinforcement schedule. Experiment II showed that, in the goal section, the effect of the drug on the PREE was due to its presence during acquisition and was not due to state dependency; but the effect of the drug in the start section was consistent with state dependency of the PREE. In Experiment III, in opposition to (1) and again in support of (2), SA given to rats trained to show patterned running for water reward on a single alternation schedule blocked patterning by increasing running speeds on nonreward trials, not by decreasing running speeds on rewarded trials.
The literature on the behavioural effects of septal and hippocampal lesions is classified accordi... more The literature on the behavioural effects of septal and hippocampal lesions is classified according to behavioural paradigm. The effects of the two kinds of lesion are summarized and compared to each other. A 'septo-hippocampal syndrome,' consisting of the effects common to both lesions, is delineated, and divergences between the effects of the two lesions are noted.
The effects of buspirone were tested on rearing in an open field. Six different doses of buspiron... more The effects of buspirone were tested on rearing in an open field. Six different doses of buspirone (10, 3.3, 1.1, 0.3, 0.1 and 0.04 mg/kg) and a single dose of chlordiazepoxide (5 mg/kg) were administered i.p. to separate groups of rats. Buspirone produced a dose-dependent decrease in rearing in the range 0.04-10 mg/kg, whereas only the higher doses (10 and 3.3 mg/kg) decreased ambulation significantly. Chlordiazepoxide reduced rearing to an extent equivalent to 1 mg/kg of buspirone. Together with data in the literature, the results suggest that 5-HT1A agonists affect rearing at lower doses than ambulation; that the effects of buspirone in the open field are similar to classical anxiolytics; and that changes in rearing may be more closely related to anxiolytic than muscle relaxant, anti-convulsant and other GABA-mediated effects of the classical anxiolytics.
The ability of the opiate antagonist, naloxone, to block the anti-conflict effects of the benzodi... more The ability of the opiate antagonist, naloxone, to block the anti-conflict effects of the benzodiazepines suggests endogenous opioid involvement in the mechanism of action of these drugs. However naloxone's ability to attenuate the effects of the benzodiazepines in animal conflict paradigms appears to be schedule specific. It is effective in acquisition of a differential reinforcement of low rates of response (DRL) schedule but not in acquisition of a non-reward successive discrimination schedule. We tested the effects of naloxone and chlordiazepoxide on acquisition of DRL and on acquisition of a version of the same schedule (signalled DRL) which was like successive discrimination in having an explicit visual signal of non-reward. Chlordiazepoxide (5 mg/kg i.p.) impaired DRL responding by increasing burst responding and premature responding close to the criterion interval. Naloxone (3 mg/kg i.p.) alone decreased burst and premature responding, it also blocked the effects of chlordiazepoxide. The signalled DRL schedule produced essentially similar drug effects. Clearly the critical schedule parameter determining whether naloxone will attenuate the anxiolytic actions of the benzodiazepines is not the presence or absence of an explicit signal of conflict.
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Papers by N. McNaughton