| Research Summary |
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We have demonstrated that the biogenic amine systems, in particular the dopaminergic (DAergic) system, play a role in buffering biological or psychological adversity. We have found evidence that the therapeutic effects of antipsychotic drugs (APDs) and other psychotropic agents may be mediated by these buffer systems, and we have shown that the mesocorticolimbic DA pathway mediates a restitutive system that exerts neuroleptic-like effects on behavior in response to chronic stress. We are also studying receptor-mediated repetitive jaw movements in rats as an animal model of oral dyskinesias in humans. This functional model of the inhibitory action of the D2 system on the D1 is a model compensatory or restitutive system.
Additional studies address mechanisms underlying adaptive responses to chronic APD treatment, going beyond the receptor to studies of possible important restitutive changes. We are further elucidating the role of c-fos and other immediate early genes in the longer term adaptive effects of typical and atypical APDs and chronic stress. Inasmuch as we previously found that the restitutive or protective processes important in maintaining mental stability produced enduring changes, it seemed that these processes probably involve changes in gene expression. Using monozygotic twins discordant for schizophrenia, all of which were found to be expressed by the "well" but not the "sick" twin. These findings are consistent with the adaptive/restitutive or protective hypothesis that we previously proposed, i.e., protective factors may be active in the well twin. We will further characterize these subtracted genes and also assess their relevance to schizophrenia by studying their expression in normal subjects and schizophrenic patients.
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| Research Information |
Research Interests | Neurobiological Studies of Serious Mental Illness | Research Keywords | adaptation, buffer systems in the brain, dopamine, neuroleptic disease model, schizophrenia |
