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Decreased haloperidol‐induced potentiation of zif268 mRNA expression in the nucleus accumbens shell and the dorsal lateral striatum of rats lacking cholecystokinin‐A receptors
Author(s) -
Shilling P.D.,
Feifel D.
Publication year - 2002
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.10028
Subject(s) - nucleus accumbens , striatum , cholecystokinin , long term potentiation , haloperidol , neuroscience , dorsum , chemistry , receptor , biology , dopamine , anatomy , biochemistry
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. Synapse 43:134–138, 2002. © 2001 Wiley‐Liss, Inc.