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Modification of quasi-morphine withdrawal with serotonin agonists and antagonists: evidence for a role of serotonin in the expression of opiate withdrawal

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Abstract

Methylxanthines produce a quasi-morphine withdrawal syndrome (QMWS) in opiate naive rats. Additionally, methylxanthine-induced suppression of conditioned behavior in rats is reversed by the alpha2 adrenergic agonist clonidine which also attenuates true opiate withdrawal and the QMWS. Therefore, the operant behavioral effect of 3-isobutyl-1-methylxanthine (IBMX) provide a model with which to study mechanisms involved in the expression of opiate withdrawal. In order to examine the role of serotonin (5-HT) in the rate-decreasing effects of IMBX on operant behavior, the 5-HT precursor 5-hydroxytryptophan, and 5-HT reuptake blocker fluoxetine were administered in combination with IBMX to rats performing a, fixed-ratio 30 operant for food reinforcement. Both drugs failed to reverse the behavioral suppression caused by relatively low doses of IBMX, suggesting that elevated 5-HT neurotransmission contributes to, rather than attenuates, the QMWS. The relatively selective 5-HT2 antagonists mianserin and pirenperone blocked the IBMX-induced suppression, whereas the classic 5-HT antagonist methysergide had no effect. The results indicate that the operant behavioral effects of IBMX and possibly the QMWS may be mediated by serotonergic mechanisms.

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  1. Mark S. Kleven

    Present address: Department of Pharmacological and Physiological Sciences, The University of Chicago, Chicago, IL, USA

Authors and Affiliations

  1. Department of Pharmacology, University of Minnesota Medical School, 435 Delaware Street S.E., 55455, Minneapolis, MN, USA

    Mark S. Kleven & Sheldon B. Sparber

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  1. Mark S. Kleven
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Kleven, M.S., Sparber, S.B. Modification of quasi-morphine withdrawal with serotonin agonists and antagonists: evidence for a role of serotonin in the expression of opiate withdrawal. Psychopharmacology 98, 231–235 (1989). https://doi.org/10.1007/BF00444696

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  • DOI: https://doi.org/10.1007/BF00444696

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