Blockade of neurotensin receptors affects differently hypo-locomotion and catalepsy induced by haloperidol in mice.
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.
Casti
Paola
P
Neuroscienze S.c.a r.l., Cagliari, Italy.
Marchese
Giorgio
G
Casu
Gianluca
G
Ruiu
Stefania
S
Pani
Luca
L
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*
D018492:Dopamine Antagonists; D007093:Imidazoles; D011720:Pyrazoles; D011804:Quinolines; D018028:Receptors, Neurotensin; C104418:SR 142948A; C079087:SR 48692; D006220:Haloperidol; D000218:Adamantane