Intact 5HT neuroterminals are not required for 5HT2 receptor down-regulation by amitriptyline.

Chronic treatment of rats with the antidepressant, amitriptyline, resulted in a reduced number of cerebral cortical 5HT2 receptors measured as cinanserin displaceable [3H] spiperone binding. Pretreatment of rats with the serotonergic neurotoxin, p-chloroamphetamine, did not inhibit the effects of subsequent chronic amitriptyline treatment on 5HT2 receptor density whilst still severe neuroterminal destruction. It is suggested that such data indicate a post-synaptic locus of action for amitriptyline and have implications in regard to current concepts of antidepressant action.