Effects of antidepressants on morphine withdrawal

ABSTRACT

The acute and chronic effects of paroxetine and fluoxetine on naloxone- withdrawal-induced place aversion in morphine dependent rats were investigated. Acutely administered fluoxetine [25 mg/kg, s.c., given 30 min prior to naloxone withdrawal pairing] and chronic daily paroxetine [10 mg/kg, s.c.] co-administration 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 fluoxetine [10 mg/kg, s.c.] co-administration with morphine did not modify subsequent withdrawal place aversion. Previous radiologand binding studies have indicated that fluoxetine has opioid-displacing properties. It is suggested therefore that acute fluoxetine 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