Decreased haloperidol-induced Potentiation of zif268 mRNA expression in the nucleus Accumbens shell and the dorsal lateral striatum of rats lacking cholecystokinin-A receptors

Evidence suggests that endogenous cholecystokinin (CCK), a neuropeptide that modulates brain dopamine function, may contribute to the therapeutic and motor effects of antipsychotic drugs via activation of CCK-A receptors in the mesolimbic and nigrostriatal pathways, respectively. To determine if CCK modulates the effects of antipsychotic drugs through CCK-A receptors, we measured the haloperidol-induced zif268 mRNA response in the nucleus accumbens (NA) shell, NA core, and dorsal lateral striatum (DLS) in Otsuka Long Evans Tokushima Fatty (OLETF) rats that lack CCK-A receptors due to a spontaneous mutation. OLETF rats and normal Long Evans rats were treated with subcutaneous (s.c.) injections of saline or haloperidol (2 mg/kg). In situ hybridization was performed and zif268 mRNA expression was quantified. The haloperidol-induced expression of zif268 mRNA was significantly decreased in the DLS (P < 0.01) and the NA shell (P < 0.05), but not in the NA core, in OLETF rats compared to LETO rats. These data suggest that CCK-A receptor mechanisms may contribute to the therapeutic and the extrapyramidal motor effects associated with antipsychotic drug treatment. (C) 2001 Wiley-Liss, Inc.