LOCOMOTOR EFFECTS OF [D-TRP(11)]NEUROTENSIN AND DOPAMINE TRANSMISSIONIN RATS

Intracerebroventricular (i.c.v.) administration of [D-Trp11]neurotensi n to rats decreased locomotor activity at a low dose (30 ng) and incre ased it at a high dose (750 ng). Only this high dose increased the dop amine turnover in the nucleus accumbens. The locomotor stimulant effec t elicited by this high dose was potentiated by the dopamine uptake in hibitor, GBR 12783 [2-(diphenyl-methoxy)ethyl]4-(3-phenyl-2-propenyl) piperazine) (5 mg/kg, i.p.), and reduced by the dopamine releaser, dex amphetamine (1.5 mg/kg). It was suppressed by the bilateral injection of 6-hydroxydopamine (8 mug/2 mul) into the nucleus accumbens when rat s were tested 4 days after the lesion. Fifteen days after the lesion, the i.c.v. administration of 750 ng of [D-Trp11]neurotensin induced hy polocomotion during the first hour of the test, and hyperlocomotion du ring the second hour. This latter locomotor stimulant effect was suppr essed by the dopamine antagonist, haloperidol (50 mug/kg, i.p.). Thus, the hypokinetic effect of 30 ng [D-Trp11]neurotensin is independent o f dopamine transmission, whereas the hyperkinesia elicited by 750 ng p roceeds via an increase in dopamine transmission in the nucleus accumb ens.