Evidence for the Involvement of Dopamine D1 and D2 Receptors in Mediating the Decrease of Food Intake during Repeated Treatment with Amphetamine

Repeated treatment with amphetamine (AMPH), a well-known anorectic agent, into animals could induce anorexia on day 1 and produce a gradual reversion of food intake (tolerant anorexia) on the following days. It is unknown whether these feeding changes are related to dopamine (DA) and/or noradrenergic neurotransmission. Thus, the present study investigated the subtype of receptor mediating AMPH-induced anorexia. Daily food intake was measured after various drugs were given. Pretreatment with haloperidol, an antagonist of DA receptors, may lead to inhibition of AMPH-induced anorexia. However, pretreatment with the α-adrenoceptor antagonist phentolamine, and the β-adrenoceptor antagonist propranolol, failed to modify the action of AMPH, suggesting the involvement of DA receptors but not adrenoceptors in the action of AMPH-induced anorexia. Furthermore, pretreatment with SCH 23390 at a dose sufficient to block D1 receptors or pimozide at a dose sufficient to inhibit D2 receptors blocked AMPH-induced anorexia, indicating the involvement of D1 and D2 receptors. In a study of tolerant anorexia, repeated treatment with the D1/D2 agonist apomorphine, but not the D1 agonist SKF 38393 or D2 agonist quinpirole, induced an AMPH-like tolerant feeding response, providing evidence for conjoint action of D1 and D2 receptors in the effect. The present results suggest that both D1 and D2 receptors are involved in anorexia and tolerant anorexia induced by chronic intermittent administration of AMPH.