DELAYED EMERGENCE OF ANTI-DEPRESSANT EFFICACY FOLLOWING WITHDRAWAL IN OLFACTORY BULBECTOMIZED RATS

Repeated antidepressant treatment attenuates the step-down passive avoidance deficit which is induced by olfactory bulbectomy in rats. Using a shuttlebox passive avoidance procedure, the effects of antidepressants were investigated after various drug withdrawal intervals. Imipramine, amitriptyline, doxepin, bupropion and mianserin were effective at 48 and usually 72 h after withdrawal, but no significant attenuation of the deficit was seen 4 h after withdrawal from any antidepressant tested. At least 4-7 days of imipramine treatment were required for efficacy. A high dose of d-amphetamine (5 mg/kg) produced similar results while tranylcypromine and haloperidol were inactive at all withdrawal intervals tested. The olfactory bulbectomy syndrome may reflect functional serotonin deficiency, which would be ameliorated through antidepressant-induced alterations in serotonin receptor sensitivity.