Attenuation of morphine dependence and withdrawal in rats by venlafaxine, a serotonin and noradrenaline reuptake inhibitor

The effects of venlafaxine, a novel serotonin and adrenaline reuptake inhib itor, on the morphine withdrawal and activation of morphine conditioned pla ce preference (CPP), were investigated in rats. Our results showed that the most morphine withdrawal signs, including jumping, writhing, shakes, explo ring, lacrimation, piloerection, irritability, and diarrhea, were attenuate d by pretreatment with 10 or 20 mg/kg venlafaxine. To investigate the effec ts of venlafaxine on relapse to opiate dependence, the morphine CPP was use d and a dopamine D2 antagonist sulpiride was selected as a control drug. Th e morphine CPP disappeared following a 28-day drug-free period and appeared again after given a single injection of 1 mg/kg morphine. Acute treatment with sulpiride (25 or 50 mg/kg, i.p.) 30 min prior to 1 mg/kg morphine inje ction significantly blocked the reacquisition of CPP, while venlafaxine (10 or 20 mg/kg, i.p.) did not show significant effect. However, chronic treat ment with venlafaxine (5 or 10 mg/kg, i.p. twice, daily, for seven consecut ive days) significantly attenuated the reacquisition of morphine CPP, where as chronic treatment with sulpiride (10 or 20 mg/kg, i.p.) have no signific ant effect. Our results demonstrated for the first time that venlafaxine st rongly attenuates morphine withdrawal and morphine-induced reaquisition of CPP in rats and suggest that venlafaxine. an effective novel antidepressive drug, may have therapeutic potential in treatment and prevention of relaps e to opiate dependence. (C) 2001 Elsevier Science Inc. All rights reserved.