RESTRICTED EATING WITH WEIGHT-LOSS SELECTIVELY DECREASES EXTRACELLULAR DOPAMINE IN THE NUCLEUS-ACCUMBENS AND ALTERS DOPAMINE RESPONSE TO AMPHETAMINE, MORPHINE, AND FOOD-INTAKE

Weight loss is known to alter food intake and drug self-administration , but the neural basis of this is unknown. Therefore, we studied effec ts of weight loss on neurochemistry of a brain mechanism involved in b ehavior reinforcement. In rats reduced 20-30% below normal weight, bas al extracellular dopamine (DA) in the nucleus accumbens (NAC) decrease d up to 50% (p < 0.01), as measured by in vivo microdialysis. No such change was observed in dorsal striatum (STR) or medial prefrontal cort ex. In underweight rats, systemic amphetamine (1.5 mg/kg i.p.) transie ntly restored extracellular DA, but only to basal normal levels. Morph ine (20 mg/kg i.p.) or a meal also increased DA, but the percent incre ase was significantly smaller in underweight than normal weight animal s. Amphetamine infused locally by reverse dialysis in the NAC increase d extracellular DA more in underweight animals than controls, suggesti ng that DA had accumulated in the presynaptic terminals. This was conf irmed by finding significantly more DA in homogenized NAC micropunches of underweight rats. Receptor counts in micropunches and quantitative receptor autoradiography showed H-3-SCH23390 and H-3-spiperone D-1- a nd D-2-type binding in the NAC, STR, frontal cortex and hypothalamus d id not change significantly. Locomotor activity was depressed suggesti ng that low DA release in the NAC may be related to energy conservatio n during weight loss. Low extracellular DA may also underlie the incre ase in food and drug intake typically observed in underweight animals and humans when they attempt to restore extracellular DA levels by nat ural or artificial means.