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.
Shilling
P D
PD
Department of Psychiatry, University of California, San Diego, California 92093, USA.
Feifel
D
D
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002766:Cholecystokinin / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D051766:Early Growth Response Protein 1; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006220:Haloperidol / Q000494:pharmacology*; D017874:Immediate-Early Proteins; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D020334:Rats, Inbred OLETF; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000172:deficiency / Q000187:drug effects* / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D014150:Antipsychotic Agents; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; D014157:Transcription Factors; D002766:Cholecystokinin; D006220:Haloperidol