Regulation of neurotensin receptor mRNA expression by neuroleptics in the rat midbrain dopaminergic neurons

The tridecapeptide neurotensin is a putative neurotransmitter in the central nervous system. Studies with experimental animals show that neurotensin interacts with dopaminergic neurons. And it is proposed that neurotensin is involved in the pathophysiology of some neuropsychiatric disorders thought to be related to malfunction of the dopaminergic system. The receptor for neurotensin has been molecularly cloned from rat brain. Uhl and Kuhar reported that the density of this receptor is increased in substantia nigra of humans treated chronically with typical neuroleptics. In this study, we found that two weeks of haloperidol (1 mg/kg/day), but not clozapine (20 mg/kg/day), chlorpromazine (10 mg/kg/day), thioridazine (10 mg/kg/day) increased neurotensin receptor mRNA levels in the rat substantia nigra and ventral tegmental area. We have examined the expression of neurotensin receptor mRNA using in situ hybridization techniques with an ³⁵S-labeled antisense RNA probe (302 bp) complementary to this receptor cDNA. Clinically, haloperidol treatment lead to a high incidence of extrapyramidal side effects. The mechanisms responsible for their differential incidence of extrapyramidal side effect are uncertain. Neurotensin and its signal transduction system may, in part, contribute to the pathophysiology of the extrapyramidal side effects from chronic haloperidol treatment by affecting dopaminergic system.