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

Life Sci. 2001 May 25;69(1):37-46. doi: 10.1016/s0024-3205(01)01096-7.


The effects of venlafaxine, a novel serotonin and adrenaline reuptake inhibitor, on the morphine withdrawal and activation of morphine conditioned place preference (CPP), were investigated in rats. Our results showed that the most morphine withdrawal signs, including jumping, writhing, shakes, exploring, lacrimation, piloerection, irritability, and diarrhea, were attenuated by pretreatment with 10 or 20 mg/kg venlafaxine. To investigate the effects of venlafaxine on relapse to opiate dependence, the morphine CPP was used and a dopamine D2 antagonist sulpiride was selected as a control drug. The 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 injection significantly blocked the reacquisition of CPP, while venlafaxine (10 or 20 mg/kg, i.p.) did not show significant effect. However, chronic treatment with venlafaxine (5 or 10 mg/kg, i.p. twice, daily, for seven consecutive days) significantly attenuated the reacquisition of morphine CPP, whereas chronic treatment with sulpiride (10 or 20 mg/kg, i.p.) have no significant effect. Our results demonstrated for the first time that venlafaxine strongly attenuates morphine withdrawal and morphine-induced reaquisition of

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Uptake Inhibitors / pharmacology*
  • Animals
  • Conditioning, Psychological
  • Cyclohexanols / pharmacology*
  • Dopamine Antagonists / pharmacology
  • Exploratory Behavior / drug effects
  • Male
  • Morphine Dependence / drug therapy
  • Morphine Dependence / physiopathology*
  • Motor Activity / drug effects
  • Norepinephrine / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Selective Serotonin Reuptake Inhibitors / pharmacology*
  • Substance Withdrawal Syndrome / drug therapy
  • Substance Withdrawal Syndrome / physiopathology*
  • Sulpiride / pharmacology
  • Venlafaxine Hydrochloride


  • Adrenergic Uptake Inhibitors
  • Cyclohexanols
  • Dopamine Antagonists
  • Serotonin Uptake Inhibitors
  • Venlafaxine Hydrochloride
  • Sulpiride
  • Norepinephrine