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Blockade of Neurotensin Receptors Affects Differently Hypo-Locomotion and Catalepsy Induced by Haloperidol in Mice

Blockade of Neurotensin Receptors Affects Differently Hypo-Locomotion and Catalepsy Induced by Haloperidol in Mice

Paola Casti, Giorgio Marchese, Gianluca Casu, Stefania Ruiu, Luca Pani

Neuropharmacology. 2004 Jul;47(1):128-35.

PMID: 15165840

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP184162218	SR 142948A		184162-21-8	Price

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