EFFECTS OF CHRONIC HALOPERIDOL AND CLOZAPINE TREATMENT ON NEUROTENSINAND C-FOS MESSENGER-RNA IN RAT NEOSTRIATAL SUBREGIONS

Previous studies have shown elevation of neurotensin neuro-medin N (NT /N) and c-fos mRNA in the dorsolateral region of the rat neostriatum ( DLSt) by acute administration of only typical antipsychotic drugs. How ever, NT/N mRNA in the nucleus accumbens-shell is enhanced acutely by several clinically efficacious antipsychotic drugs, regardless of thei r motor side effect liability. In the present study, induction of NT/N mRNA in the DLSt was observed again after 28 days of continuous admin istration (via osmotic minipumps) of haloperidol, but not clozapine. H owever, this response was only about 50% of that caused by acute halop eridol and c-fos mRNA levels in the DLSt were not elevated after the c hronic treatment. An acute challenge of haloperidol 24 hr after chroni c haloperidol treatment did not affect the tolerant response of NT neu rons but caused a small increase in c-fos mRNA in the DLSt. Similar to the DLSt, chronic haloperidol (but not clozapine) significantly enhan ced NT/N gene expression in the ventrolateral striatum, a region thoug ht to be involved in abnormal oral movements, perhaps related to tardi ve dyskinesia. Interestingly, dopamine D2 receptor binding using [I-12 5]iodosulpride nearly doubled in all regions of the striatum after chr onic haloperidol but not clozapine. In contrast to the lateral neostri atum, NT/N mRNA expression in the nucleus accumbens-shell was elevated similarly by chronic treatment with haloperidol and clozapine to a le vel observed after acute haloperidol treatment. These results demonstr ate further that region-specificity of NT/N mRNA regulation discrimina te between typical and atypical antipsychotic drugs.