Chronic amitriptyline potentiates feeding induced by intrahypothalamic norepinephrine injections.

Feeding responses to microinjections of 37 nmol norepinephrine (NE) into the medial hypothalamus of rats were assessed before and after chronic amitriptyline treatment (AMI, 10 mg/kg twice daily for 21 days). AMI-treated rats showed a 55% increase in NE-induced feeding over their pre-treatment baseline. Control rats which received daily vehicle injections showed only a non-significant 3% increase on retests. These results are consistent with recent evidence suggesting that chronic AMI may enhance the responsivity of postsynaptic alpha adrenoceptors. The data also suggest that altered hypothalamic NE mechanisms may contribute to the enhanced appetite changes reported by patients undergoing long-term AMI treatment.