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The role of serotonergic receptors in the effects ofmu opioids in squirrel monkeys responding under a titration procedure

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Abstract

This experiment was conducted to determine whether drugs acting on brain serotonin modulate the effects of themu opioid, morphine, as measured by the squirrel monkey shock titration procedure and, if so, whether serotonergic modulation is mediated via specific 5HT receptor subtypes. Under this procedure, electric shock was delivered to the monkey's tail and scheduled to increase once every 15 s from 0.01 to 2.0 mA in 30 steps. Five responses on a lever during the 15-s shock period terminated the shock for 15 s, after which the shock resumed at the next lower intensity. The intensity below which monkeys maintained shock 50% of the time (median shock level or MSL) and rate of responding (RR) in the presence of shock were determined under control conditions and after administration of morphine alone and in combination with various serotonergic compounds. Morphine increased median shock level and decreased rate of responding in a dose-dependent manner. These effects of morphine were attenuated by the 5HT1A receptor agonists, 8-OH-DPAT [(+)-8-hydroxy-2(di-n-propylamino tetralin HBr] and ipsapirone. The effects of morphine were not altered by the 5HT1A receptor antagonist, NAN-190 [1-(2-methoxyphenyl)-4-[4-(2-phthalimido) butyl] piperazine HBr], the 5HT2 receptor antagonist, ketanserin, the 5HT3 receptor antagonist, MDL 72222 [3-tropanyl-3,5-dichlorobenzoate], the alpha2 adrenergic antagonist, yohimbine, or the alpha2 adrenergic agonist, clonidine. These results suggest that 5HT1A receptors may be involved in the effects of morphine in the shock titration procedure, whereas 5HT2, 5HT3 and alpha2 adrenergic receptors do not appear to play a role in morphine's effects in this procedure.

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  1. K. R. Powell

    Present address: Department of Pharmacology, Emory University School of Medicine, 30322, Atlanta, GA, USA

Authors and Affiliations

  1. Department of Psychology, University of North Carolina at Chapel Hill, 27599-3270, Chapel Hill, NC, USA

    K. R. Powell & L. A. Dykstra

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This work was supported by US Public Health Service Grants R37 DA 02749 and F31 DA 05537 from the National Institute on Drug Abuse. Animals used in this study were cared for in accordance with the guidelines of the Institutional Animal Care and Use Committee of the University of North Carolina and the “Guide for the Care and Use of Laboratory Animals” (Department of Health and Human Services, National Institutes of Health, Publication No. 85–23, revised 1985)

Supported by Predoctoral Training Award T32 DA 07244 and recipient of Individual Predoctoral Fellowship Award F31 DA 05537 from the National Institute on Drug Abuse

Recipient of Research Scientist Award DA 00033 from the National Institute on Drug Abuse

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Powell, K.R., Dykstra, L.A. The role of serotonergic receptors in the effects ofmu opioids in squirrel monkeys responding under a titration procedure. Psychopharmacology 126, 42–49 (1996). https://doi.org/10.1007/BF02246409

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  • DOI: https://doi.org/10.1007/BF02246409

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