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.

The present study tested whether rats release more accumbens dopamine (DA) during a sugar binge when they are underweight vs. normal weight. Since acetylcholine (ACh) in the nucleus accumbens (NAc) normally increases as a meal progresses and satiety ensues, we also tested whether ACh release is altered when an animal has lost weight. Rats were maintained on daily 8-h access to chow, with 10% sucrose solution available for the first 2 h. Microdialysis performed on day 21, at normal body weight, revealed an increase in extracellular DA to 122% of baseline in response to drinking sucrose. Extracellular ACh peaked at the end of the meal. Next, the rats were food and sucrose restricted so that by day 28 they were at 85% body weight. When retested, these animals released significantly more DA when drinking sucrose (179%), but ACh release failed to rise. A control group was tested in the same manner but given sugar only on days 1, 21 and 28. At normal body weight, control animals showed a non-significant rise in DA when drinking sucrose on day 21. On day 28, at 85% body weight, the controls showed a small increase (124%) in DA release; however, this was significantly lower than the 179% observed in the underweight rats with daily sugar access. These findings suggest that when an animal binges on sugar and then loses weight, the binge releases significantly more DA and less ACh than when animals are at a normal body weight.

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impulse (17). Our results cannot be attributed to the experimental procedure itself, since identically treated control animals that received immunoglobulins from nonmyasthenic humans showed none of the myasthenic features. Furthermore, dialysis performed during preparation of the immunoglobulin fraction would remove any residual anticholinesterase medication from the patients' serums.Our study differs from the many previous attempts to transfer myasthenia gravis to animals over the past three decades (6) in at least two important respects which contributed to the present positive results: (i) We exposed the test animals to the serum factor for a relatively prolonged time, in contrast to the minutes or hours previously attempted. (ii) We used more sensitive electrophysiological and radiometric methods to detect the myasthenic abnormalities rather than relying on clinical weakness or decremental responses, which are often absent.The nature of the myasthenia-producing serum factor has not yet been elucidated, but the 33 percent ammonium sulfate fraction used in these experiments contains the immunoglobulins as well as other serum proteins (18). Whether the antibody that binds to ACh receptor (3) is itself the transferable serum factor in myasthenic patients remains to be determined. Our experiments may provide the critical link between such an antibody and the pathogenesis of myasthenia gravis as a humorally mediated autoimmune disease.

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