American Neuropsychiatric Association (ANPA)
TitleSignaling and circuitry of sensorimotor gating
InvestigatorRonald P. Hammer
Other Investigators
Brief AbstractThe long-range goal of the project is to determine the specific cellular and molecular targets related to sensorimotor gating deficits in schizophrenia. An animal model of sensorimotor gating is used to examine the neuroadaptive responses leading to recovery of disrupted prepulse inhibition (PPI) following chronic drug treatment. In contrast to the disrupting effect of acute dopamine agonist treatment, we have shown that repeated treatment attenuates the behavioral disruption by desensitizing dopamine D2-like receptors. The specific aims of the project are (1) to determine whether functional downregulation of dopamine D2-like receptors induced by chronic treatment with a D2-like receptor-selective agonist attenuates disruption of PPI in a time- and dose-dependent manner by acting in the nucleus accumbens (NAc), (2) to ascertain whether reduction of inhibitory G proteins in the NAc is sufficient to attenuate disruption of PPI, and (3) to define and characterize the subset of NAc neurons whose function is altered following chronic D2-receptor agonist treatment using retrograde labeling and immunohistochemical detection of an immediate early gene marker. The results advance our understanding of sensorimotor gating deficits in schizophrenia from the regional level to the cellular and molecular levels, and may provide novel therapeutic targets for future development.
Inclusion/Exclusion Criteria
Opportunities for CollaborationAssays of G protein function in human subjects with schizophrenia.

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