Presynaptic alpha-adrenoceptors and the action of tricyclic antidepressant drugs in behavioural despair in rats.

The influence of the alpha-adrenolytics, yohimbine and phentolamine, given in low doses thought to block presynaptic alpha-adrenoceptors, on the action of the tricyclic antidepressants imipramine, nortriptyline and amitriptyline in the behavioural despair test was investigated in Wistar rats. Antidepressant drugs given in a single dose or for 2 weeks reduced immobility in rats. Yohimbine potentiated the effect of nortriptyline or amitriptyline administered in a single dose and the effect of imipramine and amitriptyline given for 2 weeks. The potentiating effect of phentolamine was observed only in rats receiving a single dose of nortriptyline. Yohimbine given chronically for 3 weeks together with antidepressants counteracted the effect of imipramine and nortriptyline on behavioural despair. Similarly clonidine abolished the reduction of immobility induced by antidepressants given in a single dose. It is concluded that the despair test is a behavioural model which is sensitive to the noradrenergic component of the drugs and that the blockade of presynaptic alpha-adrenoceptors facilitates the action of tricyclic antidepressants in this test.