Evidence for the involvement of dopamine D-1 and D-2 receptors in mediating the decrease of food intake during repeated treatment with amphetamine

Repeated treatment with amphetamine (AMPH), a well-known anorectic agent, i nto animals could induce anorexia on day 1 and produce a gradual reversion of food intake (tolerant anorexia) on the following days. It is unknown whe ther these feeding changes are related to dopamine (DA) and/or noradrenergi c neurotransmission. Thus, the present study investigated the subtype of re ceptor mediating AMPH-induced anorexia. Daily food intake was measured afte r various drugs were given. Pretreatment with haloperidol, an antagonist of DA receptors, may lead to inhibition of AMPH-induced anorexia. However, pr etreatment with the alpha -adrenoceptor antagonist phentolamine, and the be ta -adrenoceptor antagonist propranolol, failed to modify the action of AMP H, suggesting the involvement of DA receptors but not adrenoceptors in the action of AMPH-induced anorexia. Furthermore, pretreatment with SCH 23390 a t a dose sufficient to block D-1 receptors or pimozide at a dose sufficient to inhibit D-2 receptors blocked AMPH-induced anorexia, indicating the inv olvement of D-1 and D-2 receptors. In a study of tolerant anorexia, repeate d treatment with the D-1/D-2 agonist apomorphine, but not the D-1 agonist S KF 38393 or D-2 agonist quinpirole, induced an AMPH-like tolerant feeding r esponse, providing evidence for conjoint action of D-1 and D-2 receptors in the effect. The present results suggest that both D-1 and D-2 receptors ar e involved in anorexia and tolerant anorexia induced by chronic intermitten t administration of AMPH. Copyright (C) 2001 National Science Council, ROC and S. Karger AG, Basel.