Reduced dopamine clearance in food‐restricted rats is normalized by amphetamine

Abstract

Changes in nutritional status and in circulating insulin can affect dopamine (DA) neurotransmission. This study characterized DA transporter (DAT) activity and the behavioral effects of amphetamine (AMPH) in food-restricted (10 g/day) rats. On alternate days (9–16 of food restriction) rats received saline or 1.78 mg/kg of AMPH prior to 30-min sessions in which locomotion was measured; chambers had different floor textures (holes or grid) for each type of conditioning session. Conditioned place preference (CPP) was assessed the next day with rats receiving saline prior to placement in a chamber equipped with a floor comprising both textures. The day after CPP testing, in vivo chronoamperometry was used to measure DA clearance in striatum. Compared to free-feeding rats, food-restricted rats had modest weight loss but no change in baseline or AMPH-stimulated locomotion. AMPH produced CPP in free-feeding rats and not in food-restricted rats, perhaps reflecting an increase or decrease in sensitivity to AMPH (the dose-response curve is an inverted-U). DA clearance was reduced in food-restricted rats that received saline in all 8 CPP conditioning sessions; however, DA clearance was normal in food-restricted rats that received every-other-day injections of AMPH. Paralleling earlier studies that showed AMPH normalizes DAT activity reduced by streptozotocin, these data confirm a role for insulin pathways in modulating DAT activity and demonstrate that the effects of AMPH vary markedly under modestly different physiologic conditions (free or restricted food access). Supported by DA14684 and DA17818 to CPF and DA018992 to LCD.