DIFFERENTIAL INDUCTION OF NEUROTENSIN AND C-FOS GENE-EXPRESSION BY TYPICAL VERSUS ATYPICAL ANTIPSYCHOTICS

Precise neural mechanisms underlying the pathophysiology and pharmacot herapy of psychotic disorders remain largely unknown. Present studies investigated the effects of various antipsychotic drugs on expression of the gene encoding the purported endogenous antipsychotic-like pepti de neurotensin (NT) in striatal regions of the rat brain. The results demonstrate that several clinically efficacious antipsychotic drugs se lectively and specifically increase expression of NT/neuromedin N (NT/ N) mRNA in the shell of the nucleus accumbens, a region of the forebra in associated with limbic systems. On the other hand, only typical ant ipsychotics that cause a high incidence of acute motor side effects in creased the expression of NT/N mRNA in the dorsolateral striatum, an e xtrapyramidal region primarily involved in motor control. In addition, it appears that distinct mechanisms may be involved in the effects of antipsychotics on NT/N gene expression in the dorsolateral striatum v ersus the accumbal shell. Thus neuroleptic-induced increases in NT/N m RNA expression in the dorsolateral striatum were preceded by a rapid a nd transient activation of c-fos mRNA, whereas none of the antipsychot ics affected c-fos mRNA expression in the accumbal shell. The anatomic al characteristics of NT/N gene expression induced by typical versus a typical antipsychotics raise the possibility that increased activity o f specific NT neurons may contribute to the therapeutic effects (NT ne urons in the accumbal shell) or motor side effects (NT neurons in the dorsolateral striatum) of these drugs.