title: Blockade of neurotensin receptors affects differently hypo-locomotion and catalepsy induced by haloperidol in mice.
abstract: Antipsychotic drug treatment increases neurotensin (NT) neurotransmission, and the exogenous administration of NT produces antipsychotic-like effects in rodents. In order to investigate whether "endogenous" NT may act as a natural occurring antipsychotic or may mediate antipsychotic drug activity, the effects of the selective NT receptor antagonists SR 48692 and SR 142948A were analyzed in different behavioural tests of locomotor activity using vehicle, amphetamine, or haloperidol in mice. SR 48692 (0.1-1 mg/kg, i.p.) and SR 142948A (0.03-0.1 mg/kg, i.p.) failed to affect mouse spontaneous locomotor activity and amphetamine-induced (2.5 mg/kg, i.p.) hyper-locomotion. However, SR 48692 (0.1 and 0.3 mg/kg, i.p.) and SR 142948A (0.03 and 0.05 mg/kg, i.p.) significantly alleviated the reduction of locomotor activity elicited by haloperidol (0.01 and 0.04 mg/kg, s.c.) in vehicle- or amphetamine-treated mice. Finally, SR 48692 (0.3 mg/kg, i.p.) and SR 142948A (0.05 and 0.1 mg/kg, i.p.) increased mouse catalepsy produced by haloperidol (0.3 mg/kg, s.c.). The present results indicate that while endogenous NT is not involved in the modulation of either mouse spontaneous locomotor activity or amphetamine-induced hyper-locomotion, it might act by enhancing the therapeutic effects of haloperidol and by attenuating the extrapyramidal side effects elicited by this antipsychotic.
authors.affiliation: Neuroscienze S.c.a r.l., Cagliari, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Casti
authors.forename: Giorgio
authors.initials: G
authors.lastname: Marchese
authors.forename: Gianluca
authors.initials: G
authors.lastname: Casu
authors.forename: Stefania
authors.initials: S
authors.lastname: Ruiu
authors.forename: Luca
authors.initials: L
authors.lastname: Pani
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002375:Catalepsy / Q000139:chemically induced / Q000503:physiopathology*; D018492:Dopamine Antagonists; D006220:Haloperidol; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology; D018028:Receptors, Neurotensin / Q000037:antagonists & inhibitors*
chemical_list: D018492:Dopamine Antagonists; D007093:Imidazoles; D011720:Pyrazoles; D011804:Quinolines; D018028:Receptors, Neurotensin; C104418:SR 142948A; C079087:SR 48692; D006220:Haloperidol; D000218:Adamantane