Analysis of dopamine D1 and D2 receptor involvement in d- and l-amphetamine-induced anorexia in rats

The concept of dopamine receptor subtypes and the recent development of selective dopamine receptor agonists and antagonists raises the possibility of specific subtype involvement in amphetamine-induced anorexia, and, furthermore, provides the means to evaluate the possibility. Using a test of palatable food consumption by nondeprived male rats, our data confirmed a more potent suppressant effect of d-amphetamine on food intake, compared to l-amphetamine (potency ratio 5.32:1). The test proved sensitive, with ED50s of 0.28 mg/kg and 1.49 mg/kg for d- and l-amphetamine, respectively. The modest anorectic effect of 0.3 mg/kg d-amphetamine was completely reversed by the selective dopamine D1 receptor antagonist, SCH 23390, but was not affected by the selective D2 receptor antagonist, sulpiride. A matched feeding-suppressant effect of 1.0 mg/kg l-amphetamine was reversed at one dose of SCH 23390, but was unaffected by sulpiride. Stronger anorectic effects produced by 1.0 mg/kg d-amphetamine and 3.0 mg/kg l-amphetamine were not antagonized either by SCH 23390 or sulpiride. The selective D1 receptor agonist, SKF 38393, produced a dose-dependent reduction in food consumption, without producing behavioural stereotypy. Unlike amphetamine, SKF 38393 is not self-administered, and therefore may provide an example of a novel pharmacological dissociation between anorectic and reinforcing effects of drug treatments mediated by dopamine receptors. Our data implicate dopamine D1 receptors in the control of feeding responses, and suggest that these receptors may mediate the anorectic effect of small-dose amphetamine treatments.