Contrasting actions of acute or chronic paroxetine and fluvoxamine on morphine withdrawal-induced place conditioning

Eur J Pharmacol. 1995 Mar 6;275(2):185-9. doi: 10.1016/0014-2999(94)00770-8.


The acute and chronic effects of paroxetine and fluvoxamine on naloxone withdrawal-induced place aversion in morphine dependent rats were investigated. Acutely administered fluvoxamine (25 mg/kg s.c. given 30 min prior to naloxone withdrawal pairing) and chronic daily paroxetine (10 mg/kg s.c.) coadministration with a morphine induction protocol, both attenuated morphine withdrawal place aversion. Conversely, acutely administered paroxetine (up to 25 mg/kg s.c.) or chronic daily fluvoxamine (10 mg/kg s.c.) coadministration with morphine did not modify subsequent withdrawal place aversion. Previous radioligand binding studies indicate that fluvoxamine has opioid-displacing properties. It is suggested therefore that acute fluvoxamine may have decreased withdrawal aversion, probably through serotonin and also, in part, via an opioid-like mechanism whereas chronic paroxetine decreased withdrawal aversion by a serotonergic mechanism, but it is not clear whether opioid systems play any role in the action of paroxetine.

Publication types

  • Comparative Study

MeSH terms

  • Analysis of Variance
  • Animals
  • Conditioning, Psychological / drug effects*
  • Disease Models, Animal
  • Drug Administration Schedule
  • Fluvoxamine / administration & dosage
  • Fluvoxamine / pharmacology*
  • Fluvoxamine / therapeutic use
  • Injections, Subcutaneous
  • Male
  • Morphine / toxicity*
  • Naloxone / metabolism
  • Paroxetine / administration & dosage
  • Paroxetine / pharmacology*
  • Paroxetine / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / metabolism
  • Serotonin Uptake Inhibitors
  • Substance Withdrawal Syndrome / drug therapy*
  • Substance-Related Disorders


  • Serotonin Uptake Inhibitors
  • Serotonin
  • Naloxone
  • Paroxetine
  • Morphine
  • Fluvoxamine