Differential effects of acute and chronic treatment with typical and atypical neuroleptics on c-fos mRNA expression in rat forebrain regions using non-radioactive in situ hybridization

The regional difference in the expression of c-fos mRNA in rat forebrain af ter either acute or chronic administration of typical (haloperidol and flup henazine) and atypical neuroleptics (clozapine and (+/-)-sulpiride) was inv estigated. Rats were injected intraperitoneally with vehicle or neuroleptic s daily for 14 days. Twenty-four hours after the last injection, the rats w ere challenged with vehicle or neuroleptics. C-fos mRNA expression was dete rmined by non-radioactive in situ hybridization. Acute treatment with typic al neuroleptics induced a remarkable induction of c-fos mRNA in the dorsola teral striatum, whereas this induction was greatly attenuated by chronic ad ministration. All neuroleptics examined induced c-fos mRNA in the shell reg ion of N. accumbens by acute administration and this expression was still e levated after chronic treatment. Since chronic neuroleptics do not induce t olerance to their antipsychotic activities, our study suggests that the she ll region of N. accumbens is an important target site for antipsychotic eff ects of neuroleptics. (C) 1999 Elsevier Science Ltd. All rights reserved.