Clonidine has a bidirectional effect on operant responding for food.

Clonidine, an alpha-noradrenergic agonist, has had inconsistent effects when administered peripherally in previous studies of feeding behavior. The present experiment was undertaken to evaluate clonidine using an operant feeding paradigm (continuous reinforcement schedule) to provide detailed data on the time course of its effects. Over an entire four-hour session, all doses of clonidine tested (25, 50, or 100 micrograms/kg) increased bar-pressing. The 50 micrograms/kg dose was most effective. An examination of the time course of responding revealed that the initial effect of clonidine was to decrease responses with the duration and magnitude of the decrease directly proportional to dose. However, clonidine also prolonged a phase of steady responding for food once the animals resumed bar-pressing, resulting in a net increase of food intake. Future investigations of clonidine should take into account the effects of increasing dose on delayed onset of feeding.