Reduced peripheral presynaptic adrenoceptor sensitivity following chronic antidepressant treatment in rats

Responses of the isolated vas deferens of the rat to clonidine (inhibition of contractions to field stimulation at 0.1 Hz) and noradrenaline (contraction of longitudinal muscle) were determined after one or 21 daily injections of the animals with desmethylimipramine, clorgyline, selegiline or tranylcypromine. Desmethylimipramine (10 mg kg-1) and clorgyline (2 mg kg-1) increased the clonidine EC50 in the isolated vas deferens after 21 but not after one daily injection(s). Tranylcypromine (5 mg kg-1) increased clonidine EC50 after both one and 21 injections and selegiline (1 mg kg-1) did not affect clonidine EC50 after either one or 21 injections. Only desmethylimipramine had a significant effect on noradrenaline responsiveness, producing an inconsistent decrease in EC50 with a consistent increase in maximum contractile response after 21 but not after one daily injection(s). Clorgyline (10(-5) M) increased the contractile response of the isolated vas deferens to field stimulation and antagonized the inhibitory effect of clonidine when added directly to the isolated tissue preparation. Neither clorgyline (5 mg kg-1), selegiline (1 mg kg-1) nor tranylcypromine (2.5 mg kg-1) affected significantly the inhibitory response to clonidine (1 microgram kg-1) on contractions of in situ sympathetically stimulated vas deferens in pithed rats. These results show that down-regulation of alpha 2-presynaptic adrenoceptors by chronic treatment with desmethylimipramine and clorgyline occurs in peripheral organs as well as in the central nervous system.