ABSTRACT
The present study was undertaken to assess if hypothalamic beta-endorphin (beta E) and/or brain mu opioid receptors are associated with 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) (50 micrograms/kg)-induced hypophagia and body weight decline in rats. Hypothalamic beta E concentrations were initially increased to 166% of controls on day 1, and then were depressed to 39% and 49% of control values on days 2 and 3, respectively. Brain mu opioid receptor number was increased 60% in TCDD-treated rats at day 3 without a change in the binding affinity. Food-restricted rats did not exhibit changes in hypothalamic beta E concentrations or brain mu opioid receptor number. These results indicate that TCDD causes early perturbations in hypothalamic beta E concentrations and brain mu receptor number, which may contribute to the mechanisms by which TCDD leads to decreased food intake and progressive weight loss.
Subject(s)
Brain/metabolism , Hypothalamus/metabolism , Polychlorinated Dibenzodioxins/pharmacology , Receptors, Opioid/metabolism , Animals , Brain/drug effects , Cell Membrane/metabolism , Enkephalin, Ala(2)-MePhe(4)-Gly(5)- , Enkephalins/metabolism , Food Deprivation , Hypothalamus/drug effects , Kinetics , Male , Rats , Rats, Inbred Strains , Receptors, Opioid/drug effects , Receptors, Opioid, mu , Reference ValuesABSTRACT
In separate experiments, nine (n = 20) and fifteen (n = 12) month old rats were treated with either 6% ethanol or 12% sucrose (to balance caloric intake) in the drinking water to examine the effect of chronic ethanol consumption on the hypothalamic-pituitary-adrenal axis of aged rats. Rats were maintained on these treatment regimens for thirty days and were killed by decapitation. Blood was collected and plasma concentrations of adrenocorticotropin (ACTH) and corticosterone were determined by radioimmunoassay. Adrenal glands were cleaned, quartered and used to test in vitro responsiveness to ACTH. Anterior pituitary glands from all 15 month old rats and one half of the nine month old rats were collected, frozen and extracted for measurement of tissue ACTH concentration. The remaining anterior pituitary glands from the nine month old rats were challenged with corticotropin releasing hormone (CRH) to test in vitro responsiveness. In nine month old rats, chronic ethanol consumption decreased plasma ACTH and corticosterone (P less than 0.05). Pituitary ACTH concentrations were unchanged in treated nine month old rats, but the amount of pituitary ACTH released in response to CRH was decreased (P less than 0.05) in rats consuming ethanol. In vitro responsiveness of the adrenal gland to ACTH in nine month old rats consuming ethanol was unchanged (P greater than 0.05). Plasma ACTH and corticosterone concentrations were also decreased in 15 month old rats chronically consuming ethanol (P less than 0.05). No differences were noted in responsiveness of the adrenal gland or in the amount of pituitary ACTH due to ethanol consumption in 15 month old rats (P greater than 0.05). The results of these experiments indicate that chronic ethanol consumption decreases hypothalamic-pituitary-adrenal function in aged rats.
