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Journal of Neuroscience, Vol 15, 6640-6650, Copyright © 1995 by Society for Neuroscience
Restricted eating with weight loss selectively decreases extracellular dopamine in the nucleus accumbens and alters dopamine response to amphetamine, morphine, and food intake
EN Pothos, I Creese and BG Hoebel
Department of Psychology, Princeton University, New Jersey 08544-1010, USA.
Weight loss is known to alter food intake and drug self-administration, but
the neural basis of this is unknown. Therefore, we studied effects of
weight loss on neurochemistry of a brain mechanism involved in behavior
reinforcement. In rats reduced 20-30% below normal weight, basal
extracellular dopamine (DA) in the nucleus accumbens (NAC) decreased up to
50% (p < 0.01), as measured by in vivo microdialysis. No such change was
observed in dorsal striatum (STR) or medial prefrontal cortex. In
underweight rats, systemic amphetamine (1.5 mg/kg i.p.) transiently
restored extracellular DA, but only to basal normal levels. Morphine (20
mg/kg i.p.) or a meal also increased DA, but the percent increase was
significantly smaller in underweight than normal weight animals.
Amphetamine infused locally by reverse dialysis in the NAC increased
extracellular DA more in underweight animals than controls, suggesting that
DA had accumulated in the presynaptic terminals. This was confirmed by
finding significantly more DA in homogenized NAC micropunches of
underweight rats. Receptor counts in micropunches and quantitative receptor
autoradiography showed 3H- SCH23390 and 3H-spiperone D1- and D2-type
binding in the NAC, STR, frontal cortex and hypothalamus did not change
significantly. Locomotor activity was depressed suggesting that low DA
release in the NAC may be related to energy conservation during weight
loss. Low extracellular DA may also underlie the increase in food and drug
intake typically observed in underweight animals and humans when they
attempt to restore extracellular DA levels by natural or artificial means.
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