Serotonin-depleting midbrain lesions do not prevent ovariectomy-induced weight gain

Abstract

Past research has shown that subdiaphragmatic vagotomy and midbrain raphe lesions are each effective in impeding the development of hypothalamic obesity while neither affects the development of genetic obesity in Zucker rats. To further test the parallels that may exist between these two manipulations on another putative obesity model, we studied the effects of midbrain raphe lesions on the development of ovariectomy-induced weight gain, previously shown to be unaffected by vagotomy. Ten adult female rats received thermal lesions of the dorsal and median raphe nuclei (RAPHE) while 7 served as sham controls (SHAM). Following a 26-day recovery period during which body weight, food intake and water intake were periodically monitored, bilateral ovariectomy (OVX) was performed on 7 RAPHEs and 4 SHAMs, with laparotomy (LAP) being performed on 3 RAPHEs and 3 SHAMs. Body weights and intake variables were monitored for an additional 58 days, then animals were sacrificed for brain histological and biochemical assessments. RAPHEs weighed less despite eating and drinking more than SHAMs throughout this study. Nevertheless, OVX rats gained more weight regardless of lesion (mean±SEMweight gain=73.9±5.5 g for RAPHE + OVX and 67.0±6.6 g for SHAM + OVX vs. 30.7±3.0 g for RAPHE + LAP and 39.7±5.5 g for SHAM + LAP). This occurred without reliable changes in the food or water intakes of either OVX subgroup. Histology confirmed that RAPHE lesions were largely localized to the dorsal and median raphe nuclei, as planned. Assays of forebrain monoamine levels revealed large (93%) depletions of serotonin, smaller depletions of norepinephrine (26%) and no effects on dopamine. The observed ineffectiveness of RAPHE lesions to impede OVX-induced weight gain supports earlier data suggesting that certain functional parallels may exist between such midbrain injury and vagotomy on different models of obesity.