Effect of alpha-2-adrenoceptor blockade on analgesia induced of different antidepressant drugs in mice

ABSTRACT

In this study, we investigated whether alpha2-adrenoceptors are involved in the antinociception induced by different classes of antidepressant drugs using the acetic acid-induced writhing test in mice. The subcutaneous [s.c.] administration of the non-selective noradrenaline and serotonin rcuptake inhibitors; imipramine and amitriptyline; the selective 5-hydroxytryptamine [serotonin] reuptake inhibitors [SSRJs]; fluoxetine and sertraline and the heterocyclic agent; trazodonc caused dose-related decrease in the number of abdominal constrictions [writhings] caused by intraperitoneal [i.p.] injection of dilute acetic acid in mice. The acute analgesia induced by amitriptyline, sertraline and trazodone was blocked by co-administration of the alpha2-adrenoceptor antagonist yohirnbine [4 or 8 mg/kg]. In contrast, alpha-2 blockade enhanced imipramine-induced an1inociception. Meanwhile, yohimbine administration at 4 mg/kg bu1 not 8 mg/kg significantly reduced the fluoxetine-induced analgesia. These data suggest that alpha2-adrenoceptors mediate the analgesic effect of some antidepressant drugs independent of their effect on neurotransmitter release. The present data also suggest that distinct routes mediate the analgesic effect of individual agents within the same class of antidepressant drugs