Effect of muscimol on haloperidol-induced alteration of neurotensin gene expression in the striatum and nucleus accumbens in the rat.
Acute neuroleptic administration increases the expression of neurotensin/neuromedin (NT/N) gene in rat dorsolateral striatum and shell sector of the nucleus accumbens. The purpose of this study was to examine modulation of neuroleptic induction of NT/N and the proto-oncogene c-fos expression by the GABAA agonist muscimol. Adult male Sprague-Dawley rats were treated with saline, haloperidol (1 mg/kg); muscimol (3.2 mg/kg); or haloperidol (1 mg/kg) plus muscimol (3.2 mg/kg). Animals were sacrificed 1 h after drug administration. Expression of NT/N and c-fos mRNA was examined by in situ hybridization using 35S-antisense probes. Muscimol alone had no measurable effect on basal levels of NT/N or c-fos mRNA in either the dorsolateral striatum or the nucleus accumbens. However, co-administration of muscimol with haloperidol reduced haloperidol-induced increases in NT/N as well as c-fos mRNA in the dorsolateral striatum. In contrast, NT/N mRNA expression in accumbal shell induced by haloperidol was not modulated by co-administration of muscimol. These data suggest that GABAA receptors may be involved in regulation of NT/N gene expression in the DLSt, but not in the nucleus accumbens.
Decker
K P
KP
Harborview Medical Center, University of Washington, Seattle 98104, USA.
Roy-Byrne
P P
PP
Merchant
K M
KM
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D018755:GABA Agonists / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D009118:Muscimol / Q000494:pharmacology*; D009496:Neurotensin / Q000235:genetics*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D014150:Antipsychotic Agents; D018755:GABA Agonists; D012333:RNA, Messenger; D009118:Muscimol; D009496:Neurotensin; D006220:Haloperidol