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 alpha(1) antagonist), WB-4101 (a selective alpha(1A) antagonist), yohimbine (an alpha(2) antagonist), WAY-100635 (a selective 5-HT(1A) antagonist), and ketanserin (a 5-HT(2) 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, 20 mg.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 5 mg.kg(-1) and at over 10 mg.kg(-1), respectively. These reductions were nearly complete at 20 mg.kg(-1). On the other hand, both SSRIs induced significant reductions in the licking time only at 20 mg.kg(-1). Prazosin, WB-4101, and ketanserin significantly antagonized the antinociceptive effect of 10 mg.kg(-1) of imipramine. However, imipramine-induced antinociception was not affected by yohimbine and WAY-100635. Prazosin and ketanserin also significantly suppressed antinociception by 5 mg.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 alpha(1) adrenoceptors and 5-HT(2) receptors are predominantly involved in imipramine- and desipramine-induced antinociception.