Thomas S. Rieg

β-endorphin and dynorphin abnormalities in rats subjected to exercise and restricted feeding : relationship to anorexia nervosa ?

Exercise and the endogenous opioids have been linked to anorexia nervosa. This investigation determined the effects of the weight-loss syndrome induced by voluntary exercise (22.5 h/day) in food-restricted rats (1.5 h/day food access) on the endogenous opioids. The animals were tested under resting-fed and 2-deoxy-D-glucose (2DG) stimulated conditions. Weight-matched, freely fed exercised and ad libitum fed unexercised groups served as controls. Specific opioid abnormalities were found in the syndrome. These included a basal elevation in plasma beta-endorphin, which was abnormally suppressed by 2DG, and 2DG-induced elevations in arcuate hypothalamic beta-endorphin content and supraoptic hypothalamic dynorphin-A content. None of these changes occurred in controls. Finally, it was found that short-term moderate exercise itself chronically reduced adenohypophysial beta-endorphin content and elevated supraoptic dynorphin-A content. The relationship of the syndromes hyperendorphinism to the hypothalamo-pituitary-adrenal axis and the auto-addiction hypothesis of anorexia nervosa was considered, as was the significance of the supraoptic dynorphin-A abnormality to the hypothalamo-neurohypophysial system. The differential sensitivity of the supraoptic dynorphin-A system compared to the arcuate hypothalamic beta-endorphin system to moderate exercise was also discussed.

Fluoxetine induces vasopressin and oxytocin abnormalities in food-restricted rats given voluntary exercise: relationship to anorexia nervosa

Anorexia nervosa is associated with vasopressin, oxytocin and serotonin abnormalities. Because of the relationship between exercise and anorexia nervosa, we explored the weight-loss syndrome produced by wheel running in food-deprived rats. Its effects on regional vasopressin and oxytocin concentrations were determined under basal conditions and following systemic fluoxetine. Weight-matched, exercised and unexercised rats served as controls. Fluoxetine caused abnormalities in suprachiasmatic vasopressin and dynorphin A content and in thymus oxytocin content that did not occur in weight-matched or exercised controls. No syndrome-specific anomalies occurred in the hypothalamo-neurohypophysial system or dorsal vagal complex (DVC). However, weight reduction and fluoxetine increased circulating vasopressin; moderate exercise caused fluoxetine-induced elevations in posterior pituitary vasopressin and oxytocin; and, unlike the other groups, fluoxetine increased DVC oxytocin in freely fed unexercised rats. It was concluded that syndrome-specific vasopressin and oxytocin abnormalities occur that are not secondary to weight loss or moderate exercise; that weight loss or fluoxetine increases circulating vasopressin; that moderate exercise alters neurohypophysial vasopressin and oxytocin content; and that weight loss or exercise inhibits a fluoxetine-stimulated increase in DVC oxytocin. Finally, it was argued that the fluoxetine abnormalities indicate possible serotonin dysfunction in the syndrome.

Systemic clonidine increases feeding and wheel running but does not affect rate of weight loss in rats subjected to activity-based anorexia

Activity-based anorexia (ABA) is an animal model of anorexia nervosa with two characteristics of the disorder, decreased food intake and increased activity. We have shown that chronic noradrenergic stimulation of the paraventricular hypothalamus exacerbates ABA rather than ameliorates it. This study determined if peripheral chronic administration of clonidine affects ABA. Rats were implanted SC with osmotic minipumps infusion 0, 30, or 300 micrograms/kg/day of clonidine and exposed to ABA (1.5 h/day ad lib food, 22.5 h/day ad lib wheel access). Results showed that clonidine did not affect the rate of weight loss during ABA, but increased food intake at the lower dose and wheel activity at the higher dose. It is proposed that increased energy expenditure due to wheel running is counteracted by an inhibition of sympathetically mediated diet-induced thermogenesis, and that the elevation in running by the higher dose potentially increases the risk of developing ABA.

Paraventricular hypothalamic clonidine increases rather than decreases susceptibility to activity-based anorexia in the rat

Anorexia has been related to reduced activity of the paraventricular hypothalamic (PVN) noradrenergic-feeding system. In this study we determined whether clonidine (an alpha 2-adrenergic agonist) infused into the PVN reduced susceptibility to activity-based anorexia (ABA) in the rat. In Experiment 1, clonidine (6 doses) was chronically infused into the PVN of male Sprague-Dawley rats. All animals were exposed to ABA (1.5 hr/day food access; 22.5 hr/day running wheel access) until a 25% body weight loss was reached. Dose-related increases in susceptibility to ABA and decreases in food intake were observed. In Experiment 2, for which heavier animals and 3 doses of clonidine were used, we found no difference in food intake and wheel activity but increased susceptibility to ABA. Chronic clonidine infused into the PVN does not produce hyperphagia and exacerbates rather than attenuates susceptibility to ABA.

Fluoxetine induced insulin-like growth factor II (IGF-II) changes in hypothalami of normal, exercised and food restricted rats

Hypothalamic and pituitary insulin-like growth factor II (IGF-II) peptide concentrations are differentially regulated by factors associated with metabolism such as insulin and glucoprivation. However, the effects of other metabolic stressors such as food restriction or exercise on hypothalamic IGF-II concentrations remain largely to be explored. In order to assess whether metabolic stress alters central nervous system IGF-II secretion, peptide analysis was conducted in rats exhibiting activity-based anorexia (ABA) compared to exercised-matched, body weight-matched or ad libitum fed controls. Further, the possibility of serotonergic control of IGF-II secretion was examined by determining IGF-II response to fluoxetine (FLX) injections (15 mg/kg body wt., i.p.). While ABA and body weight loss altered peripheral IGF-II concentrations compared to ad libitum fed or exercised controls, these treatments had no effect on hypothalamic or posterior pituitary IGF-II content. However, FLX administration increased IGF-II concentrations in the ventromedial hypothalamus and decreased IGF-II content in the lateral hypothalamus compared to vehicle injected. Anterior pituitary levels of IGF-II were also decreased by FLX. These data suggest that a serotonergic influence on CNS IGF-II exists and that IGF-II secretion may be altered by factors affecting serotonin metabolism or efficacy.

Rostral Hypothalamic Fetal Transplants Reduce Activity-Based Anorexia in Rats with Lesions Aimed at the Suprachiasmatic Nucleus

There is considerable interest in the relationship between exercise and anorexia nervosa/1/.