BLUNTING OF THE NEUROTENSIN MESSENGER-RNA RESPONSE TO HALOPERIDOL IN THE STRIATUM OF AGING RATS - POSSIBLE RELATIONSHIP TO DECLINE IN DOPAMINE D2-RECEPTOR EXPRESSION

Neuroleptic drugs such as haloperidol (H) induce a rapid increase in n eurotensin/neuromedin N (NT/N) gene expression in the dorsolateral str iatum (DLSt) and nucleus accumbens (NA) in young adult rats. This effe ct may be mediated by post-receptor effectors that are activated by do pamine D2 receptor antagonism. The regional pattern of induction of ne urotensin gene expression correlates with the side effect profile of p articular neuroleptics. As motor side effects of H differ in aged anim als, we hypothesized that the regional expression of the neurotensin g ene may differ between young and old animals. We administered H or sal ine acutely to 3, 14, and 25 month-old Fischer 344 rats, followed by i n situ hybridization and quantitative autoradiography for NT/N mRNA. T here was a significant age effect on the H-induced NT/N mRNA response in the DLSt, but not the NA, of older animals. In addition to the blun ted NT/N mRNA response, significant decreases in D2 receptor mRNA were observed in the lateral striatum of another group of young, middle-ag ed, and aged rats. Age-related blunting of the NT/N mRNA response to H in the DLSt may be due in part to a decrease in D2 receptors in this structure.