Acute withdrawal-related hypophagia elicited by amphetamine is attenuated by pretreatment with selective dopamine D1 or D2 receptor antagonists in rats

- Longer-term hypophagia (LTH) occurred 19-26 hours after amphetamine (AMPH) in rats
- Pretreatment with dopamine D1 or D2 receptor antagonists reduced AMPH-elicited LTH
- Dopamine receptor activation due to AMPH is an early event leading to LTH

After receiving 2.0 mg/kg amphetamine, rats show two phases of reduced food intake, short-term hypophagia, during the first several hours after treatment, and longer-term hypophagia, approximately 19 to 26 h after treatment. The longer-term hypophagia may be an indicator of an acute withdrawal. This study assessed whether D1 and D2 receptor activation were important early events in the elicitation of longer-term hypophagia. Throughout a series of five-day tests, rats could lever press for food pellets for one-hour periods beginning every 3 h. On test day 1, rats were given a saline pretreatment, and 15 min later they were given a saline treatment. On test day 3, they were given a pretreatment of either saline or a selective dopamine receptor antagonist, and 15 min later they were given a treatment of either saline or amphetamine (2.0 mg/kg). In Experiment 1, pretreatments included 3, 12, 31, and 50 μg/kg of the selective D1 receptor antagonist SCH 23390. In Experiment 2, pretreatments included 25, 50, and 100 μg/kg of the selective D2 receptor antagonist eticlopride. Distance moved was monitored for the first 6 h following pretreatment-treatment combinations to obtain an indirect behavioral measure of receptor blockade (antagonist attenuation of amphetamine hyperactivity). Food intake at each meal opportunity was monitored throughout each five day test. Patterns of food intake following day 1 saline-saline and day 3 pretreatment-treatment were compared. The combination saline-amphetamine produced short-term and longer-term hypophagia. Combinations involving antagonist-saline did not produce longer-term changes in food intake. Pretreatment with 12 to 50 μg/kg of SCH 23390 produced substantial blockade of amphetamine hyperactivity and prevented amphetamine-induced acute-withdrawal-related longer-term hypophagia. Eticlopride produced a partial blockade of longer-term hypophagia. Both D1 and D2 receptor activation are required for full expression of longer-term hypophagia following amphetamine administration.