Search PubMed⌕ Search

Biomedical subjects

H Anisman

Publications and source records attributed to H Anisman.

At least 73 records · Page 4Linked to original sources
PubMed1998

Stressor-induced corticotropin-releasing hormone, bombesin, ACTH and corticosterone variations in strains of mice differentially responsive to stressors.

The effects of brief stressor exposure on hypothalamic-pituitary-adrenal (HPA) functioning was assessed in two strains of mice shown to be differentially responsive to stressors. Mild stress (1 min of cold swim, 20 C) led to marked elevations of plasma ACTH and corticosterone concentrations in the stress-reactive BALB/cByJ and the stress-resistant C57Bl/6ByJ mice. Moreover, it was observed that the strains differed in basal CRH content within the amygdala and the paraventricullar nucleus (PVN). Within 1 min of cold swim, the CRH changes were detected in these brain regions in BALB/cByJ mice, but were less apparent in C57Bl/6ByJ mice. Following a chronic stressor regimen, the marked elevations of plasma ACTH associated with acute stressors in BALB/cByJ mice were diminished. In contrast, in C57Bl/6ByJ mice in which acute stressors hardly affected ACTH concentrations, the chronic stressor regimen lead to a marked increase of plasma ACTH. Taken together, data indicate that the stress reactivity differences seen in the two strains of mice are not limited to ACTH and corticosterone, but are also detected with respect to CRH within the amygdala and PVN. Furthermore, the suggestion is offered that the reactivity differences in the two strains of mice may have lead to different profiles of ACTH secretagogues and hence the response profile to later acute and chronic stressors differed in these strains of mice.

Adrenocorticotropic Hormone↗
PubMed1998

Efficacy and tolerability of venlafaxine in the treatment of primary dysthymia.

OBJECTIVE: Currently, there is no documentation of the efficacy of venlafaxine (a serotonin norepinephrine reuptake inhibitor) in the treatment of dysthymia. This open-label pilot investigation examined the efficacy and tolerability of venlafaxine in patients with primary dysthymia without concomitant major depression. METHODS: Fifteen patients were treated with venlafaxine for 12 weeks, with a dose range of 75 mg to 225 mg daily (taken orally), and symptom changes were measured using standard instruments including the Hamilton Depression Rating Scale (HAM-D). RESULTS: Significant changes from pretreatment to posttreatment were observed (p < 0.001). Using the standard criteria of a 50% reduction in HAM-D scores, 73.3% of patients were rated as responders. About two-thirds of the patients reported adverse events, which were mostly mild and brief in duration. CONCLUSION: Venlafaxine may be useful in the treatment of primary dysthymia but placebo-controlled studies are required for confirmation.

Adult↗
PubMed1997

Effects of interleukin-1beta and mild stress on alterations of norepinephrine, dopamine and serotonin neurotransmission: a regional microdialysis study.

The effects of systemically administered interleukin-1beta (1.0 microg) on in vivo variations of monoamines was assessed in several brain regions. Administration of the cytokine provoked a modest increase of extracellular 5-HIAA and HVA from the nucleus accumbens, and 5-HIAA from the hippocampus. Following mild neurogenic stressor (application of a series of air puffs), a still greater increase of accumbal 5-HIAA and HVA was evident, a transient increase of hippocampal 5-HT was noted and the 5-HIAA increases were augmented. Additionally, while the air puff stress was without effect on DOPAC and HVA in the prefrontal cortex of saline treated rats, a significant rise of these metabolites was apparent in rats treated with the cytokine. It appears that interleukin-1 administration may have effects on forebrain monoamines, and also results in greater neuronal reactivity to mild neurogenic stressors. This study reveals that although effects of neurogenic stressors (air puffs) and cytokine (somatic stressor) may share some similarities (e.g., HPA activation), the pattern of central neurochemical changes elicited by the cytokine could be distinguished from that induced by a more neurogenic stressor (air puffs), and that these effects showed selective synergism. These data also lend support to the contention that neurogenic stressors may have a much greater impact on central neurotransmission under conditions of immune activation.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1997

Influence of psychogenic and neurogenic stressors on endocrine and immune activity: differential effects in fast and slow seizing rat strains.

Variations of plasma ACTH and corticosterone, as well as splenic macrophage activity and mitogen-induced cell proliferation, were determined in rats following 15 min of either the neurogenic stressor of restraint or by a purely psychogenic stressor consisting of exposure to a ferret. The effects of these stressors were assessed in two strains of rats that were selectively bred for either Fast or Slow kindling epileptogenesis triggered in response to amygdala stimulation. The stressors differentially influenced behavioral responses, endocrine activity, and immune functioning, and these effects varied with the strain of rat. In response to restraint the Fast rats exhibited protracted struggling, while the Slow rats tended to be immobile. In contrast, upon ferret exposure the Fast rats showed greater immobility than the Slow rats. The stressors also induced marked elevations of plasma ACTH and corticosterone. Whereas the ACTH and corticosterone increases were more pronounced in response to the ferret in the Slow rats, restraint resulted in a markedly greater rise of plasma ACTH in the Fast strain. Proliferation of splenic lymphocytes in response to Con A and LPS were elevated in Fast seizing rats, while macrophage activity, as determined by oxygen burst following addition of PMA and luminol to splenic mononuclear cells, was greater in the Slow seizing strain. While neither stressor influenced cell proliferation in either the Fast or Slow rats, macrophage activity was greatly suppressed by ferret exposure only in the Slow rats. Taken together, it appears that while stressors influence behavior and immune and endocrine functioning, these effects may vary as a function of the interaction of the strain of rat and the specific type of stressor employed.

Adrenocorticotropic Hormone↗
PubMed1997

Differential effects of immunologic challenge on self-stimulation from the nucleus accumbens and the substantia nigra.

Paralleling the effects of uncontrollable stressors, systemic administration of sheep red blood cells (SRBC) provokes brain neurotransmitter alterations, including DA variations within mesocorticolimbic regions, coinciding with or slightly preceding the peak immune response. Inasmuch as stressors disrupt responding for brain stimulation from the nucleus accumbens, possibly reflecting the anhedonic consequences of stressors, the present investigation assessed whether antigenic challenge would also influence responding for brain stimulation. Sheep red blood cell administration was found to reduce responding for brain stimulation from the nucleus accumbens, without affecting performance from the substantia nigra. The alterations of self-stimulation from the nucleus accumbens occurred at times that approximated the peak immune response. These data suggest that antigenic challenge may induce anhedonic-like effects that may be secondary to central neurochemical alterations engendered by the treatment. The possibility is also entertained that antigenic challenge may be interpreted as a stressor and contribute to alterations of affect.

Animals↗
PubMed1997

Neuroendocrine measures and lymphocyte subsets in depressive illness: influence of a clinical interview concerning life experiences.

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 change in mood state (regardless of its valence) or to the stress associated with the interview procedure. Since the interview did not influence plasma cortisol, ACTH or norepinephrine, it is likely that the NK cell variations were independent of these endocrines. Although basal NK cells were elevated in the depressive group relative to controls, the extent of the NK cell increase provoked by the interview was comparable in depressive and control subjects. The failure to detect differences between these populations could not be attributed to ceiling effects precluding more pronounced alterations in the depressed subjects. Indeed, variations of circulating cell subtypes were found to be exquisitely sensitive to differences in stressor intensity. In a subset of control subjects, a more potent stressor (anticipation of an academic examination) increased the plasma endocrine levels, increased circulating NK cell number beyond that associated with the interview stress, and provoked an increase of several T cell subsets (CD3, CD4 and CD8). Evidently, while a clinical interview may be sufficiently stressful to influence circulating NK cells, the stress of such a procedure seems no greater in depressed than in control subjects. It is suggested that although depressed patients may exhibit higher basal NK levels, this effect is likely not related to increased reactivity to stressors.

Adrenocorticotropic Hormone↗
PubMed1996

Neuroimmune mechanisms in health and disease: 2. Disease.

In the second part of their article on the emerging field of neuroimmunology, the authors present an overview of the role of neuroimmune mechanisms in defence against infectious diseases and in immune disorders. During acute febrile illness, immune-derived cytokines initiate an acute phase response, which is characterized by fever, inactivity, fatigue, anorexia and catabolism. Profound neuroendocrine and metabolic changes take place: acute phase proteins are produced in the liver, bone marrow function and the metabolic activity of leukocytes are greatly increased, and specific immune reactivity is suppressed. Defects in regulatory processes, which are fundamental to immune disorders and inflammatory diseases, may lie in the immune system, the neuro endocrine system or both. Defects in the hypothalamus-pituitary-adrenal axis have been observed in autoimmune and rheumatic diseases, chronic inflammatory disease, chronic fatigue syndrome and fibromyalgia. Prolactin levels are often elevated in patients with systemic lupus erythematosus and other autoimmune diseases, whereas the bioactivity of prolactin is decreased in patients with rheumatoid arthritis. Levels of sex hormones and thyroid hormone are decreased during severe inflammatory disease. Defective neural regulation of inflammation likely plays a pathogenic role in allergy and asthma, in the symmetrical form of rheumatoid arthritis and in gastrointestinal inflammatory disease. A better understanding of neuroimmunoregulation holds the promise of new approaches to the treatment of immune and inflammatory diseases with the use of hormones, neurotransmitters, neuropeptides and drugs that modulate these newly recognized immune regulators.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Neuroimmune mechanisms in health and disease: 1. Health.

A novel scientific discipline that examines the complex interdependence of the neural, endocrine and immune systems in health and disease has emerged in recent years. In health, the neuroimmunoregulatory network is fundamental to host defence and to the transfer of immunity to offspring; the network also plays important roles in intestinal physiology and in tissue regeneration, healing and reproduction. The proliferation of lymphocytes in primary lymphoid organs (bone marrow, bursa of Fabricius [in birds] and thymus) and in secondary lymphoid organs (spleen, lymph nodes and mucosal lymphoid tissue) depends on prolactin and growth hormone. These hormones allow immune cells to respond to antigen and to soluble mediators, called cytokines. Immune-derived cytokines are capable of inducing fever and of altering neuro-transmitter activity in the brain and hormone secretion by the pituitary gland. The activation of the hypothalamus-pituitary-adrenal axis by cytokines leads to immunosuppression. Lymphoid organs are innervated, and tissue mast cells respond to neurologic stimuli. In general, acetylcholine and substance P exert immunostimulatory and proinflammatory effects, whereas epinephrine and somatostatin are immunosuppressive and anti-inflammatory. In this article, the authors predict that novel approaches to immunomodulation will be possible by altering the level or efficacy of immunoregulatory hormones and neurotransmitters.

Humans↗
PubMed1996

Primary dysthymia: a study of several psychosocial, endocrine and immune correlates.

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), reduced uplifts, as well as particular reliance on emotion-focused rather than problem-oriented coping strategies. Interestingly, among dysthymics, the early onset group exhibited a greater degree of hassles and greater emotion-focused coping compared to the late onset subgroup. Although hassles and coping styles were correlated with depressed mood, only coping styles predicted severity of depressed affect. It seems that although dysthymia is characterized by increased hassles and reduced uplifts, these variables do not distinguish between the severity of the depressive affect, whereas the coping styles employed in the face of the increased hassles and reduced uplifts are more closely aligned with depression severity. Dysthymia was associated with elevated levels of circulating natural killer (NK) cells. Since levels of plasma cortisol, ACTH or norepinephrine were not increased in the dysthymic subjects, it is likely that the elevated NK cell number was unrelated to these neuroendorcrine measures. In control subjects circulating NK cells were inversely related to the severity of hassles recently encountered, while in dysthymic patients stress and coping factors were unrelated to NK cell numbers. Thus, it appears that the altered NK cells in dysthymic patients were not related to the increased stress perception and altered coping which characterize these patients.

Adaptation, Psychological↗
PubMed1996

Interleukin-2 decreases accumbal dopamine efflux and responding for rewarding lateral hypothalamic stimulation.

Systemic administration of interleukin-2 (IL-2) provoked marked alterations of responding for rewarding brain stimulation from the medial forebrain bundle (MFB). In particular, when animals were tested for ICSS immediately following IL-2 treatment only a modest disturbance of responding was evident. However, if animals were subsequently exposed to repeated daily ICSS sessions (24-168 h) in the drug-free state, rightward shifts in the rate intensity functions and significant increases in reward thresholds were apparent. These results were dependent upon the presence of IL-2 during the initial ICSS session. If animals were tested for ICSS 24 h after IL-2 administration, without an intervening test, performance was unaffected. Evaluation of nonreinforced behavior after IL-2 treatment revealed that ICSS remained under stimulus control and the cytokine did not provoke reward-unrelated performance deficits. Dopamine (DA) activity in the nucleus accumbens has been implicated in goal-directed responding to positively reinforcing stimuli and in the present investigation, using in vivo microdialysis, it was observed that IL-2 markedly reduced DA release from this region. It was suggested that the protracted consequences of IL-2 on ICSS likely do not involve motoric, soporific, attentional or cognitive changes, but may be attributable to its specific actions on motivational arousal, possibly engendered by the cytokine-induced diminution of accumbal DA efflux.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

The effects of early postnatal stimulation on Morris water-maze acquisition in adult mice: genetic and maternal factors.

Following stressor exposure BALB/cByJ mice exhibit hypersecretion of corticosterone and marked brain catecholamine alterations. In addition, mice of this strain exhibit impairments of performance in a Morris water-maze, which may be exacerbated by footshock application. In the present investigation it was demonstrated that early-life handling of mouse pups (coupled with brief separation periods from the dam over the course of 21 days postpartum) reduced the learning impairments seen when mice were tested in the Morris water-maze at 120 days of age and also prevented stress-induced disturbances in this task. Likewise, cross-fostering BALB/cByJ mice with a C57BL/6ByJ dam prevented the performance deficits. In contrast, C57BL/6ByJ mice cross-fostered to a BALB/cByJ dam exhibited proficient performance. Thus, maternal factors may be important in determining the Morris water-maze disturbances, provided that this was applied on the BALB/cByJ genetic background. Stressor exposure exacerbated the performance disturbances in BALB/cByJ mice, while diazepam treatment disrupted Morris water-maze performance in both BALB/cByJ and C57BL/6ByJ mice. Paralleling the behavioral changes associated with handling, the stress-induced hypercorticosterone secretion characteristic of the BALB/cByJ mouse was attenuated by the early handling procedure. Stressor exposure also produced strain-dependent variations of NE and 5-HT, but these effects were not appreciably influenced by the handling procedure. These data are consistent with the proposition that performance disturbances of BALB/cByJ mice tested in the Morris water-maze task are associated with excessive hypothalamic-pituitary-adrenal reactivity. Moreover, it appears that the influence of early-life stimulation may interact with genetic factors in determining endocrine and behavioral stress responses.

Analysis of Variance↗
PubMed1996

Stressor-induced alterations of the splenic plaque-forming cell response: strain differences and modification by propranolol.

The effects of stressor application on the splenic plaque-forming cell (PFC) response was assessed in two strains of mice: the BALB/cByJ strain, which is highly responsive to stressors; and the more hardy DBA/2J strain. Both strains exhibited a peak PFC response 120 h following administration of sheep red blood cells (SRBC; 5 x 106 cells). Stressor exposure reduced the immune response; however, the appearance of such an outcome was dependent upon the time at which the stressor was applied relative to SRBC inoculation. In DBA/2J mice, foot-shock applied either immediately after SRBC inoculation or at the time of the peak immune response (120 h) resulted in suppression of the PFC response. In BALB/cByJ mice, both stressor severities provoked an immunosuppression when applied 120 h after inoculation, but when applied 96 h after immunization only foot-shock reduced the PFC response. At other intervals, the stressors were without effect. Pretreatment with the beta-norepinephrine antagonist propranolol precluded the immunosuppression elicited by a stressor applied 96 h after inoculation, but did not affect the reduction of the PFC response elicited by a stressor applied 120 h after inoculation. It is suggested that several factors may contribute to stressor-provoked alterations of the immune response, and that the contribution of these factors vary over the course of an immune response being mounted.

Adrenergic beta-Antagonists↗
PubMed1996

Variations of lymphocyte subsets associated with stress in depressive populations.

Major depression and dysthymia have been associated with increased perception of day-to-day stressors, greater reliance on emotion-focused coping efforts, and reduced perception of uplifting events. Moreover, it has been observed that levels of circulating natural killer (NK) cells were elevated in depressed patients. Given that mild stressors may increase circulating NK cells, it is conceivable that the elevated NK cells in depression may be secondary to the increased stress perception associated with the illness. In the present investigation a laboratory stressor, comprising a mathematical challenge, increased circulating NK cells; however, the extent of the increase was comparable in depressive, dysthymic and control subjects. Moreover, the increased NK cells induced by the stressor procedure appeared to be independent of variations of plasma cortisol, ACTH or norepinephrine. Interestingly, although the NK changes were not differentially influenced by stressors in the subject populations, in the major depressive patients correspondence existed between NK cell levels and emotion-focused coping styles. Likewise, the response to a laboratory stressor was directly related to the severity of depression and to the use of coping styles involving cognitive restructuring or problem solving.

Adaptation, Psychological↗
PubMed1995

Stress-induced disturbances in Morris water-maze performance: interstrain variability.

Marked differences were observed across strains of mice (i.e., DBA/2J, C57BL/6J, BALB/cByJ and CD-1 mice) in acquisition, performance and reversal of a place learning response in a Morris water-maze. While DBA/2J, C57BL/6J and CD-1 mice typically learned the response readily, only 20% of BALB/cByJ mice acquired the response. Commensurate with the effects of hippocampal disturbances, the performance deficits in BALB/cByJ mice were not evident when the position of the platform in the water-maze was cued. Exposure to uncontrollable foot shock did not affect the acquisition or performance of this response in the former three strains, but provoked a modest disruption of reversal performance in DBA/2J mice and markedly impaired reversal performance in BALB/cByJ mice. It seemed, however, that the response strategies adopted in these strains could be distinguished from one another. In the reversal paradigm BALB/cByJ mice initially persisted in returning to the original training quadrant rather than to the new goal quadrant. Following 2 days of training the perseveration was no longer apparent and animals seemed to adopt a random search strategy. In contrast, DBA/2J mice, which exhibited a smaller stress-induced disturbance, did not display a perseverative response style. These data suggest that inescapable shock does not disturb response-outcome associations, but may result from the induction of a perseverative response style. However, it appears that the mechanisms responsible for an interference of performance may not be uniform across strains.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Stressful life events and coping styles in relation to dysthymia and major depressive disorder: variations associated with alleviation of symptoms following pharmacotherapy.

1. Both major depression and dysthymia (chronic, low grade depression) were associated with increased reports of minor stressors (daily hassles), and feelings of loneliness, reduced uplifts, as well as the use of inappropriate coping strategies (i.e., emotion-focussed rather than problem-oriented coping). 2. Although major depressive and dysthymic patients shared several features with respect to symptomatology, dysthymics tended to report a greater number of hassles than major depressives. 3. Treatment with serotonin reuptake inhibitors over an 8-week period resulted in a marked alleviation of the depressive symptoms in both patient groups, although the clinical effectiveness of the drugs appeared somewhat later in dysthymics. 4. The attenuation of the depressive symptoms was accompanied by a modest, but significant diminution in reports of minor stressors, while the perception of uplifts remained unchanged. Moreover, recovery from depression was associated with changes in coping style, such that patients relied less on inappropriate emotion-focussed coping strategies.

Adaptation, Psychological↗
PubMed1994

Alterations in central catecholamines associated with immune responding in adult and aged mice.

Central catecholamine alterations associated with immune activity are similar to those seen following stressor exposure. Inasmuch as aged animals exhibit more pronounced stressor-provoked alterations of central amines relative to younger animals, it was of interest to determine whether immune challenge would similarly induce more pronounced central amine variations in older animals. Fifteen-month old CD-1 mice challenged with 10(7) sheep red blood cells (SRBC) revealed an equivalent peak splenic plaque-forming cell response (4 days after antigen challenge) to that of 3-month-old mice challenged with 10(6) cells. Neither plasma adrenocorticotropic hormone (ACTH) nor corticosterone levels varied over days following immunization, although ACTH levels were generally higher in the older mice. In both age groups reductions of hypothalamic and locus coeruleus norepinephrine (NE) and increased accumulation of the metabolite MHPG coincided with (or preceded by 24 h) the peak immune response. However, increased accumulation of MHPG in the hypothalamus was greater and occurred earlier in the locus coeruleus of the aged mice. Likewise, at or about the time of peak immune responses nucleus accumbens dopamine (DA) levels were reduced and metabolites elevated in both age groups, while in the prefrontal cortex only DA metabolite levels were elevated. These data are commensurate with previous findings showing that SRBC inoculation may influence central neurotransmitters and that such effects correspond with the time of the peak immune responses. Moreover, in so far as hypothalamic NE utilization is concerned, it seems that the effects of SRBC inoculation are more pronounced in aged animals.

Adrenocorticotropic Hormone↗
PubMed1994

Time-dependent in vivo mesolimbic dopamine variations following antigenic challenge.

Administration of sheep red blood cells (SRBC: 5 x 10(6)) to rats provoked an immune response which peaked 4 days following inoculation. Immune activation elicited an increase of in vivo extracellular dopamine (DA) in the nucleus accumbens, indicating increased release of DA from neurons. The DA alterations coincided with the time of the peak immune response, being significantly altered 4 days after inoculation, and declining to control levels thereafter. In contrast, the levels of serotonin metabolite, 5-hydroxyindoleacetic acid (5HIAA), were not affected by SRBC inoculation. These data are consistent with the supposition that antigenic challenge influences central neurotransmitters, and indicates that such effects are not restricted to the hypothalamus, but are apparent in mesolimbic regions. It is suggested that the antigenic challenge leads to effects comparable to those induced by stressors. As such, it might be expected that immune activation may come to produce behavioral alterations much like those engendered by stressors.

3,4-Dihydroxyphenylacetic Acid↗