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Biomedical subjects

H Anisman

Publications and source records attributed to H Anisman.

188 records · Page 11Linked to original sources

Differential effects of scopolamine and D-amphetamine on avoidance: Strain interactions.

In a discriminated Y-maze avoidance task it was observed that mice of the A/J strain were superior to mice of the DBA/2J strain, which in turn made more avoidance responses than C57BL/6J mice. Moreover, the A strain was also observed to acquire a discrimination problem more readily than either of the other strains. Administration of scopolamine enhanced active avoidance performance in A, but not DBA/2 or C57BL/6 mice. D-Amphetamine improved performance in both A and DBA/2 mice but had negligible effects on the performance of the C57BL/6 strain. Neither drug affected discrimination performance irrespective of strain. In an inhibitory avoidance task the C57BL/6 strain was found to perform more poorly than the A strain which was inferior to DBA/2 mice. Scopolamine disrupted performance in all three strains, while d-amphetamine was found to disrupt the performance of the A and DBA/2 strains only. The results were interpreted in terms of the role of associative and nonassociative effects of shock in modulating avoidance behavior.

Animals↗

Effects of d-amphetamine and scopolamine on activity before and after shock in three mouse strains.

In three experiments the following results were obtained: (a) Activity was greater both prior to and following exposure to shock among C57BL/6J mice than in DBA/2J mice, which in turn was greater than that of A/J mice. (b) Scopolamine hydrobromide increased general activity in DBA/2 and A mice, but had either no effect or decreased activity in the C57BL/6 strain. Following exposure to shock, however, the disinhibitory effects of scopolamine were apparent in all three strains. (c) d-amphetamine increased activity in all three strains. Moreover, following the single shock d-amphetamine had excitatory effects among both A and DBA/2 mice such that activity exceeded the level observed with d-amphetamine alone. Following several shock presentations a small but significant excitation was observed in C57BL/6 mice as well. Data were interpreted in terms of disinhibitory and excitatory effects of scopolamine and d-amphetamine, respectively, as well as possible interactions between the catecholaminergic and cholinergic systems. In addition, implications for sources of strain differences in avoidance behavior are discussed.

Animals↗

Dissociation of disinhibitory effects of scopolamine: strain and task factors.

In 3 experiments it was observed that 3 strains of mice (A/J, DBA/2J and C57BL/6J) differing in activity exhibited comparable levels of spontaneous alternation, and that scopolamine differentially affected activity in the strains, but uniformly eliminated shock-induced suppression and spontaneous alternation behavior. Data are discussed in terms of the relationship between activity and spontaneous alternation. It was suggested that scopolamine exerts its effects on spontaneous alternation via the effects on acetylcholine activity, independent of any effects on general activity levels.

Animals↗

Circulating lymphocyte subsets in obsessive compulsive disorder, major depression and normal controls.

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 major depressive patients, as well as from age- and sex-matched controls. Stress perception and coping styles were evaluated in order to assess whether such variables accompanied the NK alterations. Finally, in a subset of patients, symptoms of the illness, stress/coping, and circulating lymphocytes, were also evaluated following 12 weeks of antidepressant medication (serotonergic reuptake inhibitor). RESULTS: The major depressive and OCD patients reported increased perception of day-to-day stresses, coupled with reliance on emotion focused coping styles. Moreover, circulating NK cells were elevated among male OCD and major depressive patients, whereas only a modest increase of NK cells was seen in female major depressives. Twelve weeks of medication alleviated depressive and OCD symptoms, and resulted in normalization of NK cells in the major depressives. However, in OCD patients the reduction of symptoms was not accompanied by significant variations of circulating NK cells. CONCLUSIONS: Although major depression and OCD are both accompanied by elevated circulating NK cells, at least in males, normalization of NK cells following treatment was only evident in depression. The persistent elevations of NK cells among male OCD patients may reflect either a trait characteristic of the illness, or symptom reduction and not true remission. LIMITATIONS: Although elevations of lymphocyte subsets in major depressive and OCD patients were observed, conclusions concerning immune status in OCD ought to be held in abeyance pending assessment of other indices of immune and cytokine functioning.

Adaptation, Psychological↗

Do early-life events permanently alter behavioral and hormonal responses to stressors?

Early-life stimulation (e.g., brief handling) attenuates the behavioral and neuroendocrine responses to stressors encountered in adulthood, particularly with respect to activation of hypothalamic-pituitary-adrenal (HPA) activity. In contrast, if neonates were subjected to a more severe stressor, such as protracted separation from the dam or exposure to an endotoxin, then the adult response to a stressor was exaggerated. These early-life experiences program HPA functioning, including negative feedback derived from stimulation of hippocampal glucocorticoid receptors, and corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) coexpression in PVN neurons, to modify the response to subsequent stressor experiences. The persistent variations of HPA activity observed in handled/stimulated animals may stem from alterations in dam-pup interactions (e.g. increased arched-back feeding, licking, grooming). In addition genetic makeup is critical in determining stress reactivity. For instance, BALB/cByJ mice are more reactive to stressors than C57BL/6ByJ mice, exhibiting greater HPA hormonal alterations and behavioral disturbances. BALB/cByJ also fail to acquire a spatial learning response in a Morris water-maze paradigm, which has been shown to be correlated with hippocampal cell loss associated with aging. Early-life handling of BALB/cByJ mice prevented these performance deficits and attenuated the hypersecretion of ACTH and corticosterone elicited by stressors. The stressor reactivity may have been related to maternal and genetic factors. When BALB/cByJ mice were raised by a C57BL/6ByJ dam, the excessive stress-elicited HPA activity was reduced, as were the behavioral impairments. However, cross-fostering the more resilient C57BL/6ByJ mice to a BALB/cByJ dam failed to elicit the behavioral disturbances. It is suggested that genetic factors may influence dam-pup interactive styles and may thus proactively influence the response to subsequent stressors among vulnerable animals. In contrast, in relatively hardy animals the early-life manipulations may have less obvious effects.

Aging↗

Lymphocyte subsets associated with major depression and dysthymia: modification by antidepressant treatment.

Major depression and dysthymia (chronic, low grade depression) were associated with an increase in the number of CD16/56 (natural killer; NK) cells in blood, whereas other lymphocyte subsets (CD3, CD4, CD8, CD19, and the CD4/CD8 ratio) did not differ from control subjects. After treatment with a specific serotonin reuptake inhibitor, the symptoms of depression were alleviated in both the major depressive and dysthymic patients. Likewise, NK cell numbers declined to control values in these treated groups. Among the major depressive patients, the NK cell number reached control values within 4 weeks, whereas 6 months of treatment was required for such an effect to be achieved in the dysthymic patients. Although plasma levels of epinephrine, norepinephrine, cortisol, and ACTH were not different between groups, among the major depressive patients ACTH was inversely correlated with total lymphocytes, CD3, and CD19, and epinephrine was directly related to the CD4 and CD4/CD8 ratio. Among dysthymics, ACTH was unrelated to any of the lymphocyte subsets, but norepinephrine was directly related to total lymphocytes, CD3, CD4, and NK cells. The data are interpreted in terms of stress perception among major depressive and dysthymic patients and the potential impact of stressor experiences on immune processes.

1-Naphthylamine↗

Circulating lymphocyte subsets in major depression and dysthymia with typical or atypical features.

OBJECTIVE: 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). METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

Adult↗

The impact of stressors on immune and central neurotransmitter activity: bidirectional communication.

Antigenic challenge may have broad ranging effects which include not only immunological changes, but also endocrine and central neurotransmitter repercussions, and may thus elicit profound behavioral sequelae. Commensurate with the notion that bidirectional communication exists between the immune and central nervous systems it has been demonstrated that manipulations which influence central neurotransmitter or endocrine activity provoke alterations of immune functioning, and conversely immunological alterations will affect central neurotransmitter and endocrine activity. It seems, as well, that environmental stressors may provoke marked alterations of the activity of each of these systems. Indeed, in several respects the variables that influence vulnerability to stressor-provoked neurotransmitter changes, likewise affect the immunological alterations engendered by stressors. Moreover, immunological challenges will affect central neurotransmitter functioning in much the same way as stressors provoke such effects. It is thought that immune derived products (including cytokines as well as peptide hormones) may act directly or indirectly to moderate neurotransmitter functioning, and centrally derived neurotransmitters and hormones may affect receptors present on lymphocytes. In accordance with earlier suggestions, it is maintained that the immune system may be acting as a sensory organ informing the brain of the presence of antigenic challenges, and the brain may interpret such challenge as a stressor, hence leading to behavioral alterations.

Animals↗