Effects of food restriction on dopamine clearance and on behavioral effects of dopaminergic drugs in rats

Abstract

Changes in nutritional status and in circulating insulin can affect dopamine (DA) neurotransmission. This study examined the effects of food restriction (10 g/day) on DA clearance and on behavioral effects of DA drugs such as amphetamine (locomotion, conditioned place preference [CPP]), the DA receptor agonist quinpirole (yawning), and the DA receptor antagonist raclopride (catalepsy). Because repeated treatment with amphetamine can restore DA clearance in hypoinsulinemic rats, the present study also examined the effects of amphetamine on DA clearance and on the behavioral effects of quinpirole and raclopride in food‐restricted rats. Amphetamine increased locomotion similarly in free‐feeding and in food‐restricted rats; however, amphetamine produced CPP in free‐feeding and not in food‐restricted rats. Food restriction reduced DA clearance, which was restored by repeated treatment with amphetamine or by free feeding. Food restriction reduced sensitivity to quinpirole and raclopride; normal sensitivity was restored by free feeding, and not by repeated treatment with amphetamine. These data support a role for insulin in modulating DA neurotransmission and demonstrate that the effects of drugs acting on DA systems vary markedly under different physiologic (feeding) conditions. Supported by DA17918 (CPF), DA14684 (AG), and DA018992 (LCD).