Effects of serotonin-depleting midbrain lesions on the defense of hypothalamic obesity.

Previous research has suggested that lesions of the midbrain dorsal and median raphe nuclei may lower the level at which body weight is regulated in hypothalamic obesity. To test this possibility further, we examined the ability of adult female rats made obese by medial hypothalamic (MH) lesions to regain weight lost due to food deprivation after midbrain raphe lesions. We first verified that obese MH-lesioned rats would regain the weight lost during a one-week fast in the same manner as non-lesioned control rats. However, when raphe lesions were produced in both groups after a second week of fasting, the weight regain of MH-lesioned rats was impaired over a full month of access to standard laboratory chow. This deficit could not be attributed to generalized impairments in feeding or capacity to gain weight since MH + raphe-lesioned rats became hyperphagic and gained almost four times more weight than controls when subsequently allowed to consume a high fat diet. Terminal assays of forebrain serotonin, norepinephrine and dopamine revealed that raphe lesions depleted only serotonin. Furthermore, the magnitude of serotonin depletion correlated inversely with the number of days required by MH + raphe-lesioned rats to regain the deprivation-induced weight loss. These findings complement earlier observations that serotonin-depleting midbrain injury can impede the development of obesity induced by subsequent hypothalamic lesions. Both findings are compatible with the possibility that raphe lesions mitigate the elevation of body weight in hypothalamic obesity.