Evidence of a preferential role of brain serotonin in the mechanisms leading to naloxone-precipitated compulsive jumping in morphine-dependent rats

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Abstract
Various drugs acting on brain serotonin or catecholamines were administered concurrently with morphine during the development of dependence or before naloxoneprecipitated withdrawal syndrome. Of the various drugs only cyproheptadine, a serotonin antagonist, and piribedil, a dopamine agonist, reduced the frequency of jumping (but not of diarrhea or ptosis) when administered with morphine during development of dependence. When administered before naloxone, d-fenfluramine, a serotonin releaser, markedly reduced jumping, but not diarrhea and ptosis, and clonidine blocked these latter signs without affecting the frequency of jumping. Of the other drugs examined only phenoxybenzamine reduced diarrhea in morphine-abstinent rats. It is suggested that serotonin is involved in the mechanisms which lead to compulsive jumping during naloxoneprecipitated withdrawal, whereas adrenergic sites on which clonidine acts are mainly involved in the expression of signs, such as ptosis and diarrhea. No clear evidence was obtained of a role for dopamine in the withdrawal signs studied.