Chronic tranylcypromine treatment induces functional alpha 2-adrenoceptor down-regulation in rats

The effects of chronic (28 d Alzet 2002 osmotic mini-pumps) administration of antidepressant drugs on the functional sensitivity of alpha 2-adrenoceptors and on monoamine oxidase activity has been assessed. Tranylcypromine, 4-fluorotranylcypromine and clorgyline (0.5-1.0 mg kg-1) induced a decrease in the motor-suppressant effects of clonidine (50 micrograms kg-1) observed at 9-10 and 23-24 days of drug administration. These effects were associated with marked decreases in type A (clorgyline) or type A and B monoamine oxidase activity (tranylcypromine and 4-fluorotranylcypromine). The results indicate that alpha 2-adrenoceptor down-regulation is an early emergent feature of adaptive changes in noradrenaline systems induced by prolonged exposure to tranylcypromine.