ketazocine and Feeding-and-Eating-Disorders

Rats implanted with the Walker-256 (W-256) tumor exhibit marked anorexia that is most apparent at night. In this model, the hypothalamic kappa opioid system was examined for deficits that might contribute to this tumor-induced anorexia. In anorexic tumor-bearing rats (TBR), nocturnal levels of ir-DYN-8 were significantly reduced in the hypothalamus, but ir-DYN-17 levels were not. Accumulation of 3H-etorphine or 3H-ethylketocyclazocine, a putative ligand for the kappa receptor subtype, was not increased in the hypothalamus of the TBR, as might have been expected if there were less endogenous dynorphin to occupy the opioid receptors in this region. In vitro binding assays with 3H-ethylketocyclazocine indicated that dynorphin depletion in the TBR was not sufficient to increase the numbers of kappa opioid receptors in the hypothalamus. Also, the sensitivity of kappa opioid receptors involved in feeding was not altered in the TBR as indicated by an intact feeding response to ketocyclazocine. In summary, the marginal deficits of hypothalamic dynorphin in W-256 tumor-bearing rats that coincide with the phase of tumor-induced anorexia may contribute to the reduction in food intake.

Topics: Animals; Anorexia; Carcinoma 256, Walker; Circadian Rhythm; Cyclazocine; Dynorphins; Eating; Ethylketocyclazocine; Feeding and Eating Disorders; Hypothalamus; Male; Rats; Rats, Inbred Strains; Receptors, Opioid; Receptors, Opioid, kappa

Phenylpropanolamine (PPA, d,l-norephedrine), found in many over-the-counter appetite suppressants and nasal decongestants, induces anorexia by a yet unidentified mechanism. The present study evaluates the effects of PPA on different types of non-drug- and drug-induced hyperphagias (i.e., food deprivation, 2-deoxy glucose, ketocyclazocine and insulin). Phenylpropanolamine (15, 25 and 35 mg/kg IP) significantly reduced food intake in a dose-related fashion at the 1 hr and 3 hr time intervals in the food deprivation-, insulin- and 2-deoxy glucose-induced hyperphagic models. Phenylpropanolamine produced a non-dose-related 99% reduction of food intake in the ketocyclazocine-induced model at the 1 and 3 hr measurement, which was most likely due to a combination of the appetite suppressant activity of PPA and the sedation produced by ketocyclazocine in combination with PPA. We conclude that PPA is capable of suppressing appetite in rats made hyperphagic by various stimuli.

Topics: Animals; Appetite Depressants; Cyclazocine; Deoxyglucose; Dextroamphetamine; Eating; Ethylketocyclazocine; Feeding and Eating Disorders; Food Deprivation; Hyperphagia; Insulin; Male; Motor Activity; Phenylpropanolamine; Rats; Rats, Inbred Strains