zimeldine and Morphine-Dependence

This review evaluates the literature and describes an extensive series of experiments which examined the effects of zimeldine , its metabolite norzimeldine and other serotonin and norepinephrine reuptake inhibitors on voluntary ethanol consumption in rats. The results of these experiments indicate that drugs which specifically inhibit serotonin reuptake are capable of decreasing voluntary ethanol consumption. The behavioral mechanism through which these drugs exert their effects seems to be extinction of the primary reinforcing properties of alcohol. These effects seem to be partially attenuated both by drugs which modulate the norepinephrine system as well as by the serotonin postsynaptic receptor blocker methergoline. The data presented in this review are discussed in terms of the involvement of the serotonin and norepinephrine systems in the mechanism of action of these drugs. In addition, several alternative hypotheses concerning the nature of the phenomenon are offered. Finally, the implications of these data for the possible development of a treatment procedure for problem drinkers is discussed.

Topics: Alcohol Drinking; Alcohol Withdrawal Delirium; Alcoholism; Animals; Appetitive Behavior; Extinction, Psychological; Humans; Morphine Dependence; Motivation; Norepinephrine; Rats; Receptors, Adrenergic; Receptors, Serotonin; Serotonin; Serotonin Antagonists; Zimeldine

Zimelidine, a specific 5-HT uptake inhibitor, reduced peroral morphine consumption by morphine-addicted adult male and female Sprague-Dawley rats and old male rats in choice tests. The effect was dose dependent in male rats. Thus, the availability of central 5-HT appears to be important for the regulation of morphine preference in rat. The results are discussed in relation to recent literature where ethanol preference has been found to be attenuated by zimelidine. The results may provide insights into the complex cellular mechanisms underlying opiate addiction.

Topics: Animals; Dose-Response Relationship, Drug; Feeding Behavior; Female; Humans; Male; Morphine; Morphine Dependence; Quinine; Rats; Rats, Inbred Strains; Receptors, Serotonin; Zimeldine

Male Wistar rats were presented with an everyday free choice between water and a morphine-sucrose solution. Following a 5-day baseline period animals were injected with either zimelidine (10 or 20 mg/kg, i.p.), a neuronal serotonin uptake inhibitor, or Ringer's solution (2 ml/kg, i.p.) for 5 consecutive days. Treatment with zimelidine was shown to significantly attenuate morphine drinking suggesting that an increased availability of serotonin may interfere with the positive reinforcing properties of morphine. The results are also discussed in terms of a possible interaction with brain norepinephrine. The possibility that the reinforcing effects of both morphine and ethanol are subserved by common mechanisms is suggested.

Topics: Animals; Brain Chemistry; Brompheniramine; Humans; Male; Morphine Dependence; Norepinephrine; Pyridines; Rats; Self Administration; Serotonin Antagonists; Zimeldine