Locomotor effects of [D-Trp11]neurotensin and dopamine transmission in rats.
Intracerebroventricular (i.c.v.) administration of [D-Trp11]neurotensin to rats decreased locomotor activity at a low dose (30 ng) and increased it at a high dose (750 ng). Only this high dose increased the dopamine turnover in the nucleus accumbens. The locomotor stimulant effect elicited by this high dose was potentiated by the dopamine uptake inhibitor, GBR 12783 (1-[2-(diphenyl-methoxy)ethyl]4-(3-phenyl-2-propenyl) piperazine) (5 mg/kg, i.p.), and reduced by the dopamine releaser, dexamphetamine (1.5 mg/kg). It was suppressed by the bilateral injection of 6-hydroxydopamine (8 micrograms/2 microliters) into the nucleus accumbens when rats 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 hypolocomotion during the first hour of the test, and hyperlocomotion during the second hour. This latter locomotor stimulant effect was suppressed by the dopamine antagonist, haloperidol (50 micrograms/kg, i.p.). Thus, the hypokinetic effect of 30 ng [D-Trp11]neurotensin is independent of dopamine transmission, whereas the hyperkinesia elicited by 750 ng proceeds via an increase in dopamine transmission in the nucleus accumbens.
European Institute for Peptide Research, Unité de Neuropsychopharmacologie Expérimentale, URA 1170 du CNRS, UFR de Médecine et Pharmacie de Rouen, Saint Etienne du Rouvray, France.
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D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects*; D009496:Neurotensin / Q000031:analogs & derivatives* / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects*
D010879:Piperazines; D009496:Neurotensin; C039737:1-(2-(diphenylmethoxy)ethyl)-4-(3-phenyl-2-propenyl)piperazine; C024309:neurotensin, Trp(11)-; D000661:Amphetamine; D004298:Dopamine