Inconsistent results have been reported concerning circulating lymphocyte subsets in depression. ... more Inconsistent results have been reported concerning circulating lymphocyte subsets in depression. To establish whether the immune alterations in depression could be related to neurovegetative symptoms, lymphocyte subsets were assessed in major depressive and dysthymic patients who exhibited either typical or atypical features (ie, the latter characterized by mood reactivity and reversed neurovegetative features). Blood was collected from major depressive, atypical depressive, typical dysthymic, or atypical dysthymic patients and from nondepressed control subjects. Circulating lymphocyte subsets (CD3, CD4, CD8, CD19, CD16/CD56) were determined by flow cytometry. In a subset of patients, lymphocyte subsets were also determined after a 12-week course of antidepressant medication. Although T and B cell populations did not differ between the depressive subtypes and control subjects, circulating natural killer (NK) cells were elevated in depressive illness, and varied as a function of depressive subtype and sex. Among male patients, NK cells were elevated to a greater extent in typical than in atypical depression, and more so in major depressive than in dysthymic patients. Among female patients, circulating NK cells were lower than in male patients, and only among the typical major depressive patients did NK cells exceed those of controls. Normalization of NK cells occurred with successful pharmacotherapy. Depression may be associated with elevated levels of circulating NK cells. Although the neurovegetative features associated with depression, particularly altered eating, may have contributed to the elevated NK cells, depressive affect itself also contributed in this respect. However, the relative contributions of these factors varied between male and female patients.
Stress-the International Journal on The Biology of Stress, 1999
Analysis of stressor effects on immune functioning is complicated by the fact that the nature of ... more Analysis of stressor effects on immune functioning is complicated by the fact that the nature of the changes observed may be influenced by organismic factors (e.g., species, strain, age), the nature, severity and chronicity of the stressor, as well as the specific immune parameters being examined. It is demonstrated in the present investigation that in the highly reactive inbred BALB/cByJ mouse, the relatively hardy C57BL/6ByJ strain, as well as in the noninbred CD-1 strain, acute psychogenic (predator exposure) and neurogenic (footshock) stressors reduced splenic macrophage activity, and this effect was less marked after a chronic stressor. With protracted, but not transient, psychosocial disturbances (isolated housing) similar effects were seen, suggesting that the effect was not simply due to a change of the social mileau. The psychogenic and neurogenic stressors also enhanced LPS-stimulated lymphocyte proliferation in CD-1, but not in the inbred strains. However, isolated housing reduced both B and T cell proliferation, indicating that social isolation likely affects processes distinct from those of other stressors. Interestingly, when the aversiveness of the psychogenic stressor was increased (by decreasing the distance between the rat and the mouse) LPS-stimulated lymphocyte proliferation was reduced in the reactive BALB/cByJ strain, but increased in the hardy C57BL/6ByJ mice. This stressor, however, enhanced T cell proliferation in both strains of mice. It is suggested that analysis of stressor effects need to consider in greater detail the characteristics of the organism being stressed, as well as the characteristics of the stressor itself.
Background: Obsessive compulsive disorder (OCD) shares several features with depressive illness (... more Background: Obsessive compulsive disorder (OCD) shares several features with depressive illness (e.g., comorbidity, early escape from dexamethasone suppression, effectiveness of serotonergic pharmacotherapy). It was of interest to establish whether OCD, like major depression, was also associated with immune alterations, notably elevations of circulating natural killer (NK) cells. Method: Circulating lymphocytes were determined from morning blood samples taken from OCD and
The effects of a clinical interview concerning either positive or negative day-to-day events on l... more The effects of a clinical interview concerning either positive or negative day-to-day events on lymphocyte subpopulations, and on plasma cortisol, ACTH and norepinephrine, were determined in depressive patients (major depressive and dysthymic) and in normal controls. Irrespective of its content, the interview provoked an elevation of circulating natural killer (NK) cells, suggesting that this effect was related to either a
Depressive illness has been associated with variations of several aspects of immune functioning, ... more Depressive illness has been associated with variations of several aspects of immune functioning, as well as alterations of cytokine production in stimulated lymphocytes. In the present investigation we sought to determine whether pharmacologically-induced reductions of mood in healthy, male subjects would be associated with alterations in the levels of circulating IL-1β or IL-6 or to in vitro lymphocyte proliferation in
Background: Depressive illness may be associated with immune and cytokine alterations. However, d... more Background: Depressive illness may be associated with immune and cytokine alterations. However, data are unavailable concerning functional immune changes associated with chronic, low-grade depression (dysthymia). Moreover, the contribution of the neurovegetative features of depression (e.g., altered sleep, eating) to the immune alterations remains to be determined. Methods: Mitogen-stimulated cell proliferation was assessed in major depressive and dysthymic patients exhibiting either
The relationship between primary dysthymia (chronic, low grade depression) and indices of major a... more The relationship between primary dysthymia (chronic, low grade depression) and indices of major and minor life stresses, uplifts and coping styles was examined. Additionally, circulating lymphocyte subsets were assessed in dysthymic patients to determine their relationship to stress/coping factors or plasma levels of Cortisol, ACTH or norepinephrine. Primary dysthymia was found to be associated with increased minor Stressors (daily hassles),
Considerable evidence supports the view that depressive illness and suicidal behaviour stem from ... more Considerable evidence supports the view that depressive illness and suicidal behaviour stem from perturbations of neuroplasticity. Presently, we assessed whether depressed individuals who died by suicide displayed brain region-specific changes in brain derived neurotrophic factor (BDNF) and whether such effects varied by gender. Using postmortem samples from non-psychiatric controls and depressed individuals who died by suicide, BDNF protein levels were assessed within the hippocampus and frontopolar prefrontal cortex using Western blot. As expected, BDNF levels were reduced within the frontopolar prefrontal cortex among female depressed suicides; however, males showed no such effect. Contrastingly, within the hippocampus, depressed male but not female suicides displayed significant reductions of BDNF protein levels. Although the mechanisms driving the gender and brain region specific BDNF changes are unclear, our data do support the notion that complex alterations of neuroplasticit...
Ketamine, a non-competitive NMDA receptor antagonist, has historically been used as a sedative in... more Ketamine, a non-competitive NMDA receptor antagonist, has historically been used as a sedative in veterinary and human medicine. Recent reports suggest that ketamine displays anti-depressant and anxiolytic effects at sub-anaesthetic doses. Other NMDA receptor antagonists disrupt fear memory, however little work has been done on Ketamine in this regard.The objective of this study was to investigate the effects of Ketamine on reconsolidation and expression of fear memory in Sprague-Dawley rats. Using contextual and cued (tone) fear conditioning, we tested the effects of systemic ketamine (1, 3 and 10 mg/kg) or saline administered either 1) 20 min prior to memory reactivation (fear expression) or 2) immediately post-reactivation (reconsolidation) on conditioned fear (level of freezing behavior). Results showed that Ketamine (3 or 10 mg/kg; p<.05) administered prior to reactivation significantly attenuated the expression of learned fear as reflected by a reduction in freezing behavio...
The prevalence of anxiety disorders is rising rapidly in today’s society, impacted greatly by rec... more The prevalence of anxiety disorders is rising rapidly in today’s society, impacted greatly by recent times of civil unrest and war throughout the world. Many of the currently prescribed drug therapies for anxiety disorders are associated with aversive side-effects and lose efficacy with repeated administration. Ethtnobotanical research has shown that anxiolytic properties of certain plants are of therapeutic relevance in treating anxiety symptoms. The objective of the present study was to investigate the anxiolytic effects of a botanical blend ethanolic extract of a 1:1 Souroubea sympetala and Platanus occidentalis (Sycamore tree), which contains 15% of the previously identified anxiolytic principle; betulinic acid (BA). The fear potentiated startle paradigm was used for this study based on its translational relevance to post traumatic stress disorder (PTSD) as exaggerated startle is a primary symptom. By measuring the startle response of the rats, the effects of the botanical blend...
The prevalence of anxiety disorders is rising rapidly in today’s society, impacted greatly by rec... more The prevalence of anxiety disorders is rising rapidly in today’s society, impacted greatly by recent times of civil unrest and war throughout the world. Many of the currently prescribed drug therapies for anxiety disorders are associated with aversive side-effects and lose efficacy with repeated administration. Ethnobotanical research has shown that anxiolytic properties of certain plants are of therapeutic relevance in treating anxiety symptoms. The objective of the present study was to investigate the anxiolytic effects of a botanical blend ethanolic extract of a 1:1 Souroubea sympetala and Platanus occidentalis (Sycamore tree), which contains 15% of the previously identified anxiolytic principle; betulinic acid (BA). The three main facets of conditioned fear: fear memory expression, extinction and reconsolidation were investigated using the Fear Potentiated Startle (FPS) and Conditioned Emotional Response (CER) paradigms, based on their translational relevance to post traumatic s...
Stressful events have been implicated in the evolution of mood disorders. In addition to brain ne... more Stressful events have been implicated in the evolution of mood disorders. In addition to brain neurotransmitters and growth factors, the view has been offered that these disorders might be provoked by the activation of the inflammatory immune system as well as by de novo changes of inflammatory cytokines within the brain. The present review describes the impact of social stressors in animals and in humans on behavioral changes reminiscent of depressive states as well as on cytokine functioning. Social stressors increase pro-inflammatory cytokines in circulation as well as in brain regions that have been associated with depression, varying with the animal's social status and/or behavioral methods used to contend with social challenges. Likewise, in humans, social stressors that favor the development of depression are accompanied by elevated circulating cytokine levels and conversely, conditions that limit the cytokine elevations correlated with symptom attenuation or reversal. Th...
Cytokines, signaling molecules of the immune system, have been implicated in the provocation of d... more Cytokines, signaling molecules of the immune system, have been implicated in the provocation of depression. Analysis of the behavioral effects of interleukin-1beta (IL-1beta), and their modification by antidepressants, is complicated since the anorexic and anhedonic effects of the cytokine are not readily dissociated from one another. The effects of IL-1beta in male and female rats were evaluated with respect to free consumption of lab chow and responding for sucrose reward on a progressive ratio (PR) schedule. This schedule assesses motivation to respond by progressively increasing the efforts rats must expend to receive a fixed reward. Using this schedule, it was then possible to assess the influence of chronic fluoxetine in attenuating the effects of IL-1beta. The effect of a single intraperitoneal injection of IL-1beta treatment was assessed in rats trained to respond on a PR schedule for sucrose reward, and who could obtain ad lib chow. In a second experiment rats were pretreat...
The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP), 2002
Stressful events have been implicated in the provocation of depressive illness. Inasmuch as immun... more Stressful events have been implicated in the provocation of depressive illness. Inasmuch as immunological challenge, and particularly cytokine administration, engender neuroendocrine and central neurochemical changes reminiscent of those provoked by psychogenic stressors, it was suggested that immune activation may also contribute to affective illness. The present report provides a brief overview of the neurochemical sequelae of acute and repeated interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and IL-2 treatment, describes some of the synergisms associated with these treatments, as well as their potential interactions with psychogenic stressors. In addition, a discussion is provided concerning the fact that cytokines, like stressors, may have time-dependent proactive effects, so that re-exposure to the treatments provoke greatly augmented neurochemical changes (sensitization). Given that the effects of cytokines are evident within hypothalamic, as well as ext...
The effects of systemically administered interleukin-1beta (1.0 microg), interleukin-6 (1.0 micro... more The effects of systemically administered interleukin-1beta (1.0 microg), interleukin-6 (1.0 microg) and interleukin-2 (1.0 microg) on in vivo variations of monoamines were assessed in the nucleus accumbens. Administration of interleukin-1beta did not affect extracellular accumbal dopamine, provoked a modest rise of homovanillic acid, and prevented the decline of dihydroxyphenylacetic acid ordinarily seen in saline treated rats. Also, interleukin-1 provoked a modest increase of extracellular 5-hydroxyindoleacetic acid from the nucleus accumbens. Following exposure to the stress of a series of air-puffs, a still greater increase of accumbal 5-hydroxyindoleacetic acid was evident. In contrast to interleukin-1, systemic administration of interleukin-6 and interleukin-2 both induced marked reductions of interstitial dopamine levels. The air-puff exposure further enhanced these effects in rats that had received the cytokine treatment. As well, interleukin-6 and interleukin-2 were both fou...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 2003
The molecular mechanisms mediating degeneration of midbrain dopamine neurons in Parkinson's d... more The molecular mechanisms mediating degeneration of midbrain dopamine neurons in Parkinson's disease (PD) are poorly understood. Here, we provide evidence to support a role for the involvement of the calcium-dependent proteases, calpains, in the loss of dopamine neurons in a mouse model of PD. We show that administration of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) evokes an increase in calpain-mediated proteolysis in nigral dopamine neurons in vivo. Inhibition of calpain proteolysis using either a calpain inhibitor (MDL-28170) or adenovirus-mediated overexpression of the endogenous calpain inhibitor protein, calpastatin, significantly attenuated MPTP-induced loss of nigral dopamine neurons. Commensurate with this neuroprotection, MPTP-induced locomotor deficits were abolished, and markers of striatal postsynaptic activity were normalized in calpain inhibitor-treated mice. However, behavioral improvements in MPTP-treated, calpain inhibited mice did not correlate with re...
Stressor experiences during the juvenile period may increase vulnerability to anxiety and depress... more Stressor experiences during the juvenile period may increase vulnerability to anxiety and depressive-like symptoms in adulthood. Stressors may also promote palatable feeding, possibly reflecting a form of self-medication. The current study investigated the short- and long-term consequences of a stressor applied during the juvenile period on anxiety- and depressive-like behavior measured by the elevated plus maze (EPM), social interaction and forced swim test (FST). Furthermore, the effects of stress on caloric intake, preference for a palatable food and indices of metabolic syndrome and obesity were assessed. Male Wistar rats exposed to 3 consecutive days of variable stressors on postnatal days (PD) 27-29, displayed elevated anxiety-like behaviors as adults, which could be attenuated by consumption of a palatable high-fat diet. However, consumption of a palatable food in response to a stressor appeared to contribute to increased adiposity.
Drug addiction is an association of compulsive drug use with long-term associative learning/memor... more Drug addiction is an association of compulsive drug use with long-term associative learning/memory. Multiple forms of learning/memory are primarily subserved by activity- or experience-dependent synaptic long-term potentiation (LTP) and long-term depression (LTD). Recent studies suggest LTP expression in locally activated glutamate synapses onto dopamine neurons (local Glu-DA synapses) of the midbrain ventral tegmental area (VTA) following a single or chronic
Inconsistent results have been reported concerning circulating lymphocyte subsets in depression. ... more Inconsistent results have been reported concerning circulating lymphocyte subsets in depression. To establish whether the immune alterations in depression could be related to neurovegetative symptoms, lymphocyte subsets were assessed in major depressive and dysthymic patients who exhibited either typical or atypical features (ie, the latter characterized by mood reactivity and reversed neurovegetative features). Blood was collected from major depressive, atypical depressive, typical dysthymic, or atypical dysthymic patients and from nondepressed control subjects. Circulating lymphocyte subsets (CD3, CD4, CD8, CD19, CD16/CD56) were determined by flow cytometry. In a subset of patients, lymphocyte subsets were also determined after a 12-week course of antidepressant medication. Although T and B cell populations did not differ between the depressive subtypes and control subjects, circulating natural killer (NK) cells were elevated in depressive illness, and varied as a function of depressive subtype and sex. Among male patients, NK cells were elevated to a greater extent in typical than in atypical depression, and more so in major depressive than in dysthymic patients. Among female patients, circulating NK cells were lower than in male patients, and only among the typical major depressive patients did NK cells exceed those of controls. Normalization of NK cells occurred with successful pharmacotherapy. Depression may be associated with elevated levels of circulating NK cells. Although the neurovegetative features associated with depression, particularly altered eating, may have contributed to the elevated NK cells, depressive affect itself also contributed in this respect. However, the relative contributions of these factors varied between male and female patients.
Stress-the International Journal on The Biology of Stress, 1999
Analysis of stressor effects on immune functioning is complicated by the fact that the nature of ... more Analysis of stressor effects on immune functioning is complicated by the fact that the nature of the changes observed may be influenced by organismic factors (e.g., species, strain, age), the nature, severity and chronicity of the stressor, as well as the specific immune parameters being examined. It is demonstrated in the present investigation that in the highly reactive inbred BALB/cByJ mouse, the relatively hardy C57BL/6ByJ strain, as well as in the noninbred CD-1 strain, acute psychogenic (predator exposure) and neurogenic (footshock) stressors reduced splenic macrophage activity, and this effect was less marked after a chronic stressor. With protracted, but not transient, psychosocial disturbances (isolated housing) similar effects were seen, suggesting that the effect was not simply due to a change of the social mileau. The psychogenic and neurogenic stressors also enhanced LPS-stimulated lymphocyte proliferation in CD-1, but not in the inbred strains. However, isolated housing reduced both B and T cell proliferation, indicating that social isolation likely affects processes distinct from those of other stressors. Interestingly, when the aversiveness of the psychogenic stressor was increased (by decreasing the distance between the rat and the mouse) LPS-stimulated lymphocyte proliferation was reduced in the reactive BALB/cByJ strain, but increased in the hardy C57BL/6ByJ mice. This stressor, however, enhanced T cell proliferation in both strains of mice. It is suggested that analysis of stressor effects need to consider in greater detail the characteristics of the organism being stressed, as well as the characteristics of the stressor itself.
Background: Obsessive compulsive disorder (OCD) shares several features with depressive illness (... more Background: Obsessive compulsive disorder (OCD) shares several features with depressive illness (e.g., comorbidity, early escape from dexamethasone suppression, effectiveness of serotonergic pharmacotherapy). It was of interest to establish whether OCD, like major depression, was also associated with immune alterations, notably elevations of circulating natural killer (NK) cells. Method: Circulating lymphocytes were determined from morning blood samples taken from OCD and
The effects of a clinical interview concerning either positive or negative day-to-day events on l... more The effects of a clinical interview concerning either positive or negative day-to-day events on lymphocyte subpopulations, and on plasma cortisol, ACTH and norepinephrine, were determined in depressive patients (major depressive and dysthymic) and in normal controls. Irrespective of its content, the interview provoked an elevation of circulating natural killer (NK) cells, suggesting that this effect was related to either a
Depressive illness has been associated with variations of several aspects of immune functioning, ... more Depressive illness has been associated with variations of several aspects of immune functioning, as well as alterations of cytokine production in stimulated lymphocytes. In the present investigation we sought to determine whether pharmacologically-induced reductions of mood in healthy, male subjects would be associated with alterations in the levels of circulating IL-1β or IL-6 or to in vitro lymphocyte proliferation in
Background: Depressive illness may be associated with immune and cytokine alterations. However, d... more Background: Depressive illness may be associated with immune and cytokine alterations. However, data are unavailable concerning functional immune changes associated with chronic, low-grade depression (dysthymia). Moreover, the contribution of the neurovegetative features of depression (e.g., altered sleep, eating) to the immune alterations remains to be determined. Methods: Mitogen-stimulated cell proliferation was assessed in major depressive and dysthymic patients exhibiting either
The relationship between primary dysthymia (chronic, low grade depression) and indices of major a... more The relationship between primary dysthymia (chronic, low grade depression) and indices of major and minor life stresses, uplifts and coping styles was examined. Additionally, circulating lymphocyte subsets were assessed in dysthymic patients to determine their relationship to stress/coping factors or plasma levels of Cortisol, ACTH or norepinephrine. Primary dysthymia was found to be associated with increased minor Stressors (daily hassles),
Considerable evidence supports the view that depressive illness and suicidal behaviour stem from ... more Considerable evidence supports the view that depressive illness and suicidal behaviour stem from perturbations of neuroplasticity. Presently, we assessed whether depressed individuals who died by suicide displayed brain region-specific changes in brain derived neurotrophic factor (BDNF) and whether such effects varied by gender. Using postmortem samples from non-psychiatric controls and depressed individuals who died by suicide, BDNF protein levels were assessed within the hippocampus and frontopolar prefrontal cortex using Western blot. As expected, BDNF levels were reduced within the frontopolar prefrontal cortex among female depressed suicides; however, males showed no such effect. Contrastingly, within the hippocampus, depressed male but not female suicides displayed significant reductions of BDNF protein levels. Although the mechanisms driving the gender and brain region specific BDNF changes are unclear, our data do support the notion that complex alterations of neuroplasticit...
Ketamine, a non-competitive NMDA receptor antagonist, has historically been used as a sedative in... more Ketamine, a non-competitive NMDA receptor antagonist, has historically been used as a sedative in veterinary and human medicine. Recent reports suggest that ketamine displays anti-depressant and anxiolytic effects at sub-anaesthetic doses. Other NMDA receptor antagonists disrupt fear memory, however little work has been done on Ketamine in this regard.The objective of this study was to investigate the effects of Ketamine on reconsolidation and expression of fear memory in Sprague-Dawley rats. Using contextual and cued (tone) fear conditioning, we tested the effects of systemic ketamine (1, 3 and 10 mg/kg) or saline administered either 1) 20 min prior to memory reactivation (fear expression) or 2) immediately post-reactivation (reconsolidation) on conditioned fear (level of freezing behavior). Results showed that Ketamine (3 or 10 mg/kg; p<.05) administered prior to reactivation significantly attenuated the expression of learned fear as reflected by a reduction in freezing behavio...
The prevalence of anxiety disorders is rising rapidly in today’s society, impacted greatly by rec... more The prevalence of anxiety disorders is rising rapidly in today’s society, impacted greatly by recent times of civil unrest and war throughout the world. Many of the currently prescribed drug therapies for anxiety disorders are associated with aversive side-effects and lose efficacy with repeated administration. Ethtnobotanical research has shown that anxiolytic properties of certain plants are of therapeutic relevance in treating anxiety symptoms. The objective of the present study was to investigate the anxiolytic effects of a botanical blend ethanolic extract of a 1:1 Souroubea sympetala and Platanus occidentalis (Sycamore tree), which contains 15% of the previously identified anxiolytic principle; betulinic acid (BA). The fear potentiated startle paradigm was used for this study based on its translational relevance to post traumatic stress disorder (PTSD) as exaggerated startle is a primary symptom. By measuring the startle response of the rats, the effects of the botanical blend...
The prevalence of anxiety disorders is rising rapidly in today’s society, impacted greatly by rec... more The prevalence of anxiety disorders is rising rapidly in today’s society, impacted greatly by recent times of civil unrest and war throughout the world. Many of the currently prescribed drug therapies for anxiety disorders are associated with aversive side-effects and lose efficacy with repeated administration. Ethnobotanical research has shown that anxiolytic properties of certain plants are of therapeutic relevance in treating anxiety symptoms. The objective of the present study was to investigate the anxiolytic effects of a botanical blend ethanolic extract of a 1:1 Souroubea sympetala and Platanus occidentalis (Sycamore tree), which contains 15% of the previously identified anxiolytic principle; betulinic acid (BA). The three main facets of conditioned fear: fear memory expression, extinction and reconsolidation were investigated using the Fear Potentiated Startle (FPS) and Conditioned Emotional Response (CER) paradigms, based on their translational relevance to post traumatic s...
Stressful events have been implicated in the evolution of mood disorders. In addition to brain ne... more Stressful events have been implicated in the evolution of mood disorders. In addition to brain neurotransmitters and growth factors, the view has been offered that these disorders might be provoked by the activation of the inflammatory immune system as well as by de novo changes of inflammatory cytokines within the brain. The present review describes the impact of social stressors in animals and in humans on behavioral changes reminiscent of depressive states as well as on cytokine functioning. Social stressors increase pro-inflammatory cytokines in circulation as well as in brain regions that have been associated with depression, varying with the animal's social status and/or behavioral methods used to contend with social challenges. Likewise, in humans, social stressors that favor the development of depression are accompanied by elevated circulating cytokine levels and conversely, conditions that limit the cytokine elevations correlated with symptom attenuation or reversal. Th...
Cytokines, signaling molecules of the immune system, have been implicated in the provocation of d... more Cytokines, signaling molecules of the immune system, have been implicated in the provocation of depression. Analysis of the behavioral effects of interleukin-1beta (IL-1beta), and their modification by antidepressants, is complicated since the anorexic and anhedonic effects of the cytokine are not readily dissociated from one another. The effects of IL-1beta in male and female rats were evaluated with respect to free consumption of lab chow and responding for sucrose reward on a progressive ratio (PR) schedule. This schedule assesses motivation to respond by progressively increasing the efforts rats must expend to receive a fixed reward. Using this schedule, it was then possible to assess the influence of chronic fluoxetine in attenuating the effects of IL-1beta. The effect of a single intraperitoneal injection of IL-1beta treatment was assessed in rats trained to respond on a PR schedule for sucrose reward, and who could obtain ad lib chow. In a second experiment rats were pretreat...
The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP), 2002
Stressful events have been implicated in the provocation of depressive illness. Inasmuch as immun... more Stressful events have been implicated in the provocation of depressive illness. Inasmuch as immunological challenge, and particularly cytokine administration, engender neuroendocrine and central neurochemical changes reminiscent of those provoked by psychogenic stressors, it was suggested that immune activation may also contribute to affective illness. The present report provides a brief overview of the neurochemical sequelae of acute and repeated interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and IL-2 treatment, describes some of the synergisms associated with these treatments, as well as their potential interactions with psychogenic stressors. In addition, a discussion is provided concerning the fact that cytokines, like stressors, may have time-dependent proactive effects, so that re-exposure to the treatments provoke greatly augmented neurochemical changes (sensitization). Given that the effects of cytokines are evident within hypothalamic, as well as ext...
The effects of systemically administered interleukin-1beta (1.0 microg), interleukin-6 (1.0 micro... more The effects of systemically administered interleukin-1beta (1.0 microg), interleukin-6 (1.0 microg) and interleukin-2 (1.0 microg) on in vivo variations of monoamines were assessed in the nucleus accumbens. Administration of interleukin-1beta did not affect extracellular accumbal dopamine, provoked a modest rise of homovanillic acid, and prevented the decline of dihydroxyphenylacetic acid ordinarily seen in saline treated rats. Also, interleukin-1 provoked a modest increase of extracellular 5-hydroxyindoleacetic acid from the nucleus accumbens. Following exposure to the stress of a series of air-puffs, a still greater increase of accumbal 5-hydroxyindoleacetic acid was evident. In contrast to interleukin-1, systemic administration of interleukin-6 and interleukin-2 both induced marked reductions of interstitial dopamine levels. The air-puff exposure further enhanced these effects in rats that had received the cytokine treatment. As well, interleukin-6 and interleukin-2 were both fou...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 2003
The molecular mechanisms mediating degeneration of midbrain dopamine neurons in Parkinson's d... more The molecular mechanisms mediating degeneration of midbrain dopamine neurons in Parkinson's disease (PD) are poorly understood. Here, we provide evidence to support a role for the involvement of the calcium-dependent proteases, calpains, in the loss of dopamine neurons in a mouse model of PD. We show that administration of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) evokes an increase in calpain-mediated proteolysis in nigral dopamine neurons in vivo. Inhibition of calpain proteolysis using either a calpain inhibitor (MDL-28170) or adenovirus-mediated overexpression of the endogenous calpain inhibitor protein, calpastatin, significantly attenuated MPTP-induced loss of nigral dopamine neurons. Commensurate with this neuroprotection, MPTP-induced locomotor deficits were abolished, and markers of striatal postsynaptic activity were normalized in calpain inhibitor-treated mice. However, behavioral improvements in MPTP-treated, calpain inhibited mice did not correlate with re...
Stressor experiences during the juvenile period may increase vulnerability to anxiety and depress... more Stressor experiences during the juvenile period may increase vulnerability to anxiety and depressive-like symptoms in adulthood. Stressors may also promote palatable feeding, possibly reflecting a form of self-medication. The current study investigated the short- and long-term consequences of a stressor applied during the juvenile period on anxiety- and depressive-like behavior measured by the elevated plus maze (EPM), social interaction and forced swim test (FST). Furthermore, the effects of stress on caloric intake, preference for a palatable food and indices of metabolic syndrome and obesity were assessed. Male Wistar rats exposed to 3 consecutive days of variable stressors on postnatal days (PD) 27-29, displayed elevated anxiety-like behaviors as adults, which could be attenuated by consumption of a palatable high-fat diet. However, consumption of a palatable food in response to a stressor appeared to contribute to increased adiposity.
Drug addiction is an association of compulsive drug use with long-term associative learning/memor... more Drug addiction is an association of compulsive drug use with long-term associative learning/memory. Multiple forms of learning/memory are primarily subserved by activity- or experience-dependent synaptic long-term potentiation (LTP) and long-term depression (LTD). Recent studies suggest LTP expression in locally activated glutamate synapses onto dopamine neurons (local Glu-DA synapses) of the midbrain ventral tegmental area (VTA) following a single or chronic
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