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.