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J Comp Physiol Psychol. 1981 Jun;95(3):391-405.

Increased food intake, body weight, and adiposity in rats after regional neurochemical depletion of serotonin.


Long-term changes in food and water intake, body weight, and skeletal growth were assessed following bilateral hypothalamic microinfusions of the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). The analysis of ingestive behavior included assessment of photoperiodic effects and responsivity to alterations in dietary composition. The neuroanatomical and neurochemical selectivity of the serotonergic depletion was documented by regional spectrofluorometric analysis for serotonin, dopamine, and norepinephrine. The results indicated that norepinephrine and dopamine were not depleted in the brain areas examined. However, substantial depletion of serotonin occurred in the septum, hippocampus, and hypothalamus of the 5,7-DHT (12 microgram) group. During feeding of a high-fat diet, the serotonin-depleted group exhibited a long-lasting and stable hyperphagia which led to an increase in body weight. This hyperphagia occurred during both phases of the photoperiod but was disproportionately distributed, occurring to a greater extent in the light phase. Because body weight increased in the absence of increased skeletal growth or intestinal weight, it is concluded that the increased body weight reflected increased adiposity. The serotonin-depleted group also exhibited an essential light-phase hyperdipsia, increasing water intake above that which would be accounted for by the light-phase hyperphagia. Because the light-phase hyperdipsia was counterbalanced by a dark-phase hypodipsia, there was no change in the 24-hour water intake. The hyperphagia exhibited by the 5,7-DHT (12 microgram) group was associated with both hippocampal and hypothalamic serotonergic depletion. The results of this investigation provide the first clear evidence of an inhibitory role of serotonin in food intake and point to the importance of maximizing both neurochemical and neuroanatomical selectivity in such investigations.

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