Loss of amitriptyline analgesia in alpha 2A-adrenoceptor deficient mice.

Tricyclic antidepressants have analgesic and sedative effects in addition to their antidepressive properties. We tested the acute analgesic and locomotor inhibitory effects of the tricyclic antidepressant amitriptyline and the alpha(2)-adrenoceptor agonist clonidine in wild-type control and in alpha(2A)-adrenoceptor knockout mice in hot-plate and tail-flick tests. Amitriptyline-induced analgesia was lost in alpha(2A)-adrenoceptor knockout mice. The locomotor inhibitory effect of amitriptyline was reduced, but not fully abolished in alpha(2A)-adrenoceptor knockout mice. Similar results were obtained with clonidine. We conclude that alpha(2A)-adrenoceptors appear to have a significant role in amitriptyline-induced acute analgesia in mice, and that alpha(2A)-adrenoceptors also participate in the sedative effects of amitriptyline.