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Pharmacol Biochem Behav. 1988 Dec;31(4):899-904.

Effects of 5-HT and alpha 1 adrenoceptor antagonists on kappa opioid-induced sedation.

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1
Parke-Davis Research Unit, Addenbrookes Hospital Site, Cambridge.

Abstract

The kappa opioid agonists PD-117302 and U-50488 were found to produce dose-dependent reductions in spontaneous locomotor activity in mice. The magnitude of the response to a given dose of each kappa agonist was found to be clearly potentiated by pretreating the animals with either ketanserin (1 mg/kg) or prazosin (0.5 mg/kg). Pretreatment with the selective 5-HT2 receptor antagonist ritanserin given at a high dose (1 mg/kg), the nonselective 5-HT antagonist methysergide or the 5-HT synthesis inhibitor parachlorophenylalanine did not alter the magnitude of the response to the kappa agonist. These results suggest that 5-HT systems are not involved in the sedative effects of kappa opioid agonists and that the potentiating effect seen in animals pretreated with ketanserin is due to the alpha 1 blocking properties of this compound since the effect was mimicked by the alpha 1 antagonist prazosin.

PMID:
2855271
DOI:
10.1016/0091-3057(88)90402-9
[Indexed for MEDLINE]

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