Is the opioid system involved in the antinociceptive activity of antidepressants?

ABSTRACT

Antidepressants induce antinociception. The exact mechanism of this effect is not clear. In this study, induced antinociception by antidepressants [fluoxetine, fluvoxamine, sertraline, paroxetine, citalopram and zimelidine] was tested using the general opioid antagonist, naloxone and the kappa preferring antagonist, Mr2266BS. Antinociceptive activity of antidepressants in mice was assessed using the abdominal constriction assay. Briefly, acetic acid [1%] was injected intraperitoneally [ip] and the incidence [writhes] counted for 20 minutes as a criteria for nociception. The decrease of writhes, in drug administered animals compared to control group, was calculated as a percentage of control values and designated% protection[as a criteria for antinociceptive activity of the drug]. All antidepressants tested demonstrated dose-related antinociception induction. Antinociception induced by fluoxetine, fluvoxamine and sertraline was significantly reduced by naloxone and Mr2266BS. In contrast, paroxetine, citalopram and zimelidine induced antinociception not modified by these two opioid receptor antagonists. These data demonstrate an opioid-like activity for some, but not all, antidepressants