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

Abstract

Various drugs acting on brain serotonin or catecholamines were administered concurrently with morphine during the development of dependence or before naloxone-precipitated 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 naloxone-precipitated 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.

Inhibition of 5-HT Neurotransmission Increases Clonidine Protective Effects on Naloxone-induced Conditioned Place Aversion in Morphine-dependent Rats

“…However, several findings have suggested that 5-HT is not responsible for the physical symptoms of withdrawal (Blasig et al, 1976;Silverstone et al, 1993), except for a possible role in jumping behavior (Cervo et al, 1983;Way et al, 1968). For example, it has been shown that serotonergic transmission blockade, either by specific 5-HT lesion (Ho et al, 1972) or a 5-HT antagonist (Cervo et al, 1981;Samanin et al, 1980) along with chronic morphine treatment, reduces the development of jumping behavior during morphine withdrawal. Concerning the role of serotonin in the motivational aspect of morphine withdrawal, there are conflicting data.…”

Evidence that 5‐hydroxytryptamine in the forebrain is involved in naloxone‐precipitated jumping in morphine‐dependent rats

“…The present study confirms and extends these findings, showing that forebrain 5-HT may be particularly involved. Although in experiments with 5,7-DHT no distinction can be made between development and expression of jumping in morphine dependent rats, cyproheptadine and methergoline, two 5-HT antagonists (Clineschmidt & Lotti, 1974;Fuxe, Agnati & Everitt, 1975) were recently found to reduce jumping when administered concurrently with morphine during development of dependence (Cervo et al, 1981;Samanin et al, 1980) but had no effect when given immediately before naloxone-precipitated withdrawal (unpublished results). Therefore, reduced development rather than reduced expression of jumping may occur in animals with impairment of 5-HT transmission in the forebrain.…”

“…Withdrawal signs within 30 min were recorded, according to a procedure described previously (Cervo et al, 1981). The Assay of5-hydroxytryptamine Some 5,7-DHT-treated animals that had received no morphine were randomly chosen from the experimental groups and killed by decapitation.…”

“…Recent studies using 5-hydroxytryptamine (5-HT) antagonists have suggested that brain 5-HT is involved in the development of naloxoneprecipitated jumping in morphine-dependent rats (Samanin, Cervo & Rochat, 1980;Cervo, Rochat, Romandini & Samanin, 1981) and intraventricular injection of 5-HT neurotoxins was found to reduce jumping in morphine-abstinent rats (Herz & Blasig, 1978).…”

Efficacy of Buspirone in the Treatment of Opioid Withdrawal

“…Twenty-nine hospitalized heroin addicts were randomized to 4 groups: (1) placebo; (2) methadone; (3) buspirone 30 mg daily; (4) buspirone 45 mg daily. The double-blind trial started in all patients with a 5-day methadone stabilization period ending with a 30-mg dose.…”