Differential Effects of Immunologic Challenge on Self-Stimulation From the Nucleus Accumbens and the Substantia Nigra

Zacharko, Robert M.; Zalcman, Steve; MacNeil, Glenda; Andrews, Monique M.; Mendella, Paul D.; Anisman, Hymie

doi:10.1016/s0091-3057(97)00053-1

Cited by 18 publications

(8 citation statements)

References 31 publications

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“…This report was recently corroborated by the findings that exogenous administration of LPS (Borowski, Kokkinidis, Merali, & Anisman, 1997) or IL-2 (Anisman, Kokkinidis, Borowski, & Merali, 1998;Anisman, Kokkinidis, & Merali, 1996) produce a dramatic and long-lasting decrease in ICSS. Antigenic challenge with sheep red blood cells also reduced ICSS from rat nucleus accumbens at times that approximated the peak of immune response (Zacharko, Zalcman, Macneil, Andrews, Mendella, & Anisman, 1997). As shown in the above studies, the effects of immune challenges on ICSS represent a specific motivational change, rather than motoric, soporific, attentional or cognitive deficit.…”

Section: Decreased Responding For Rewarding Intracranial Self Stimulamentioning

confidence: 58%

Cytokines, “Depression Due to A General Medical Condition,” and Antidepressant Drugs

Raz

Weidenfeld

Pollak

et al. 1999

Advances in Experimental Medicine and Biology

180

118

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Section: Decreased Responding For Rewarding Intracranial Self Stimulamentioning

confidence: 58%

Cytokines, “Depression Due to A General Medical Condition,” and Antidepressant Drugs

Raz

Weidenfeld

Pollak

et al. 1999

Advances in Experimental Medicine and Biology

180

118

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“…18 This report was recently corroborated by the findings that exogenous administration of IL-2 produce a specific and long-lasting decrease in ICSS. 17,19 Administration of LPS, 20 IL-1 β , 19 or antigenic challenge with sheep red blood cells 21 was also associated with suppression of ICSS.…”

Section: Behavioral Effects Of Infectious and Autoimmune Diseases In mentioning

confidence: 97%

Illness, Cytokines, and Depression

Yirmiya

Pollak

Morag

et al. 2000

Annals of the New York Academy of Sciences

250

129

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A BSTRACT : Various medical conditions that involve activation of the immune system are associated with psychological and neuroendocrine changes that resemble the characteristics of depression. In this review we present our recent studies, designed to investigate the relationship between the behavioral effects of immune activation and depressive symptomatology. In the first set of experiments, we used a double-blind prospective design to investigate the psychological consequences of illness in two models: (1) vaccination of teenage girls with live attenuated rubella virus, and (2) lipopolysaccharide (LPS) administration in healthy male volunteers. In the rubella study, we demonstrated that, compared to control group subjects and to their own baseline, a subgroup of vulnerable individuals (girls from low socioeconomic status) showed a significant virus-induced increase in depressed mood up to 10 weeks after vaccination. In an ongoing study on the effects of LPS, we demonstrated significant LPSinduced elevation in the levels of depression and anxiety as well as memory deficits. These psychological effects were highly correlated with the levels of LPS-induced cytokine secretion. In parallel experiments, we demonstrated in rodents that immune activation with various acute and chronic immune challenges induces a depressive-like syndrome, characterized by anhedonia, anorexia, body weight loss, and reduced locomotor, exploratory, and social behavior. Chronic treatment with antidepressants (imipramine or fluoxetine) attenuated many of the behavioral effects of LPS, as well as LPS-induced changes in body temperature, adrenocortical activation, hypothalamic serotonin release, and the expression of splenic TNF-␣ mRNA. Taken together, these findings suggest that cytokines are involved in the etiology and symptomatology of illness-associated depression.

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“…We focused on IgM class antibodies because alterations in striatal activity and behavior are induced in close temporal congruity with peak IgM levels during an orchestrated immune response (Zalcman et al, 1991; Lacosta et al, 1994; Zacharko et al, 1997). …”

Section: Resultsmentioning

confidence: 99%

“…Dopamine activity returns to baseline levels after the time of the peak IgM response (i.e., as IgM titers decline). In parallel, alterations in rates of responding for intracranial self-stimulation in mesostriatal sites are induced around the time of the peak IgM response (Zacharko et al, 1997). Of further relevance, peripheral injections of a monoclonal IgM antibody directed against amyloid beta protein penetrates the blood–brain barrier (BBB) and reverses cognitive deficits in mice (Banks et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Anti-streptococcus IgM antibodies induce repetitive stereotyped movements: Cell activation and co-localization with Fcα/μ receptors in the striatum and motor cortex

Zhang

Patel

Zhu

et al. 2012

Brain, Behavior, and Immunity

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Group A beta-hemolytic streptococcus (GABHS) infections are implicated in neuropsychiatric disorders associated with an increased expression of repetitive stereotyped movements. Anti-streptococcus IgG presumably cross-reacts with elements on basal ganglia cells, modifies their function, and triggers symptoms. IgM may play a unique role in precipitating behavioral disturbances since variations in cortico-striatal activity occur in temporal congruity with peak IgM titers during an orchestrated immune response. We discovered in Balb/c mice that single subcutaneous injections of mouse monoclonal IgM antibodies to Streptococcus Group A bacteria induce marked dose-dependent increases in repetitive stereotyped movements, including head bobbing, sniffing, and intense grooming. Effects were antibody- and antigen-specific: anti-streptococcus IgG stimulated ambulatory activity and vertical activity but not these stereotypies, while anti-KLH IgM reduced activity. We suggest that anti-streptococcus IgM and IgG play unique roles in provoking GABHS-related behavioral disturbances. Paralleling its stereotypy-inducing effects, anti-streptococcus IgM stimulated Fos-like immunoreactivity in regions linked to cortico-striatal projections involved in motor control, including subregions of the caudate, nucleus accumbens, and motor cortex. This is the first evidence that anti-streptococcus IgM antibodies induce in vivo functional changes in these structures. Moreover, there was a striking similarity in the distributions of anti-streptococcus IgM deposits and Fos-like immunoreactivity in these regions. Of further importance, Fcα/μ receptors, which bind IgM, were present- and co-localized with anti-streptococcus IgM in these structures. We suggest that anti-streptococcus IgM-induced alterations of cell activity reflect local actions of IgM that involve Fcα/μ receptors. These findings support the use of anti-streptococcus monoclonal antibody administration in Balb/c mice to model GABHS-related behavioral disturbances and identify underlying mechanisms.

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Differential Effects of Immunologic Challenge on Self-Stimulation From the Nucleus Accumbens and the Substantia Nigra

Cited by 18 publications

References 31 publications

Cytokines, “Depression Due to A General Medical Condition,” and Antidepressant Drugs

Cytokines, “Depression Due to A General Medical Condition,” and Antidepressant Drugs

Illness, Cytokines, and Depression

Anti-streptococcus IgM antibodies induce repetitive stereotyped movements: Cell activation and co-localization with Fcα/μ receptors in the striatum and motor cortex

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