Enhancement of amphetamine anorexia after chronic administration of sulpiride in rats.

Long-term administration of sulpiride induces hyperphagia and obesity in female rats. After sulpiride withdrawal, a significant hypophagia has been observed. The hyperphagia could be related to the blockade and the hypophagia to supersensitivity of dopamine D2 receptors, in particular those D2 receptors located in the perifornical hypothalamus. If this were the case, an enhancement of anorexia induced by amphetamine and dopamine should be observed after interruption of long-term sulpiride treatment. Two doses of systemic sulpiride (20 or 200 mg/kg) and one dose of intrahypothalamic sulpiride (15 micrograms) were tested. Amphetamine was administered by systemic or intrahypothalamic infusion. Dopamine was administered in the hypothalamus. After withdrawal of systemic administration of sulpiride (200 mg/kg), an enhancement of anorexia induced by systemic amphetamine was observed. However, the anorexia induced by intrahypothalamic injections of amphetamine or dopamine was not affected by the interruption of the sulpiride treatment. These results suggest that the hypophagia following chronic sulpiride treatment is not due to supersensitivity of D2 dopamine receptors in the lateral hypothalamus. Moreover, the change in the response to amphetamine might be related to supersensitivity of extrahypothalamic D2 receptors.