Elsevier

Life Sciences

Volume 69, Issue 1, 25 May 2001, Pages 37-46
Life Sciences

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

https://doi.org/10.1016/S0024-3205(01)01096-7Get rights and content

Abstract

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 CPP in rats and suggest that venlafaxine, an effective novel antidepressive drug, may have therapeutic potential in treatment and prevention of relapse to opiate dependence.

References (0)

Cited by (51)

  • Nitric oxide modulates tapentadol antinociceptive tolerance and physical dependence

    2021, European Journal of Pharmacology
    Citation Excerpt :

    It is worth noting that, like chronic treatment with opioid agonists which induces adaptations in μ-opioid receptor signalling (Christie, 2008; Williams et al., 2001), continuous exposure to some inhibitors and ligands of the noradrenaline transporter can downregulate it, as revealed by studies involving cell cultures (Zhu et al., 1998, 2000; Zhu and Ordway, 1997). Moreover, in behavioural studies, pretreatment with the serotonin and noradrenaline reuptake inhibitor, venlafaxine, resulted in the attenuation of morphine dependence and withdrawal in rats (Lu et al., 2001). Therefore, it seems that changes within the noradrenergic pathway can account for the milder physical dependence signs associated with tapentadol than with morphine use.

  • Bupropion attenuates morphine tolerance and dependence: Possible role of glutamate, norepinephrine, inflammation, and oxidative stress

    2018, Pharmacological Reports
    Citation Excerpt :

    Thus, effects of bupropion on morphine-induced changes in Glu, nitrite, MDA, and GSH levels might be responsible for attenuation of morphine tolerance and dependence. Moreover, other antidepressants were reported to have similar effects on these mediators; hence, this could be the convergence point for different antidepressants’ efficacy in attenuating morphine tolerance and dependence [16–20]. Further studies are required to confirm this suggestion.

  • General Aspects of Areca Nut Addiction

    2016, Neuropathology of Drug Addictions and Substance Misuse Volume 3: General Processes and Mechanisms, Prescription Medications, Caffeine and Areca, Polydrug Misuse, Emerging Addictions and Non-Drug Addictions
View all citing articles on Scopus
View full text