Antinociceptive efficacy of antidepressants: Assessment of five antidepressants and four monoamine receptors in rats

Purpose. For assessment of the antinociceptive potency of antidepressants, we compared the antinociceptive effects of serotonin selective reuptake inhibitors (SSRIs) and classical tricyclic antidepressants (TCAs) in rats. We also attempted to elucidate the monoamine receptor subtypes predominantly involved in the antinociceptive effect of antidepressants. Methods. Male Wistar rats received SSRIs (sertraline, fluvoxamine, and citalopram) or TCAs (imipramine and desipramine) intraperitoneally, and the reaction time until pain response in the hot plate test and licking time in the formalin test were measured 60 min later. We also observed the effects of prazosin (an α1 antagonist), WB-4101 (a selective α1A antagonist), yohimbine (an α2 antagonist), WAY-100635 (a selective 5-HT1A antagonist), and ketanserin (a 5-HT2 antagonist), which were simultaneously administered with imipramine or desipramine, on the antidepressant-induced antinociceptive effect in the formalin test. Results. In the hot plate test, desipramine, 20mg·kg-1, but not imipramine or sertraline, produced a significant increase in reaction time. In the formalin test, desipramine and imipramine produced significant reductions in the licking time at over 5mg·kg-1 and at over 10mg·kg-1, respectively. These reductions were nearly complete at 20mg·kg-1. On the other hand, both SSRIs induced significant reductions in the licking time only at 20mg·kg-1. Prazosin, WB-4101, and ketanserin significantly antagonized the antinociceptive effect of 10mg·kg-1 of imipramine. However, imipramine-induced antinociception was not affected by yohimbine and WAY-100635. Prazosin and ketanserin also significantly suppressed antinociception by 5mg·kg-1 of desipramine. Conclusion. These findings suggest that classical TCAs are likely to have a therapeutic advantage over SSRIs for pain control. In addition, it is likely that central α1 adrenoceptors and 5-HT2 receptors are predominantly involved in imipramine- and desipramine-induced antinociception.