Date of Award
Doctor of Philosophy
Opiates were administered to the ventromedial hypothalamus (VMH), a brain site associated with feeding regulation, to provide some indication of the central component of opiate-induced feeding. The objectives of the investigation were to establish whether opiates given into the VMH could elicit dose-dependent feeding at stereospecific receptors, how this effect is mediated and whether changes in feeding and core temperature are interdependent. Also, feeding following injection of morphine into various brain sites was examined.;Male Sprague-Dawley rats were implanted stereotaxically with cannulae, and feeding and core temperature were monitored.;Injection of the opiates morphine and levorphanol and the quaternary opiate morphine methiodide into the VMH resulted in prolonged feeding preceded by a lengthy latency period. Noradrenaline produced only brief yet vigorous feeding.;Receptor specificity was indicated by the lack of feeding following the administration of the non-analgesic analogue of levorphanol, dextrorphan, and the reversal of morphine- and morphine methiodide-induced feeding by subcutaneous injection of the opiate antagonist, naloxone. Pre-treatment with VMH-applied naloxone was not as effective. Codeine, a weak ligand at opiate receptors, and codeine methiodide, did not induce ingestion. Only morphine (a (mu)-receptor agonist), not ketocyclazocine or phencyclidine ((kappa)- and (sigma)-opiate receptor agonists) increased ingestion.;Opioid peptides elicited feeding which was not reversed by VMH-administered naloxone. Ingestion following D-Ala('2)-D-Leu('5)-enkephalin, a (delta)-receptor ligand, was rapid in onset and ended within an hour. (beta)-Endorphin-induced feeding resembled that following morphine.;The feeding effects due to morphine and (beta)-endorphin were accompanied by changes in temperature, but levorphanol, morphine methiodide and low doses of enkephalin caused feeding without altering temperature. Small doses of (beta)-endorphin elevated temperature without altering ingestion.;Noradrenaline may mediate the feeding response to opiates since the (alpha)-adrenergic antagonist, phentolamine, blocked ingestion while the (alpha)(,2)-adrenergic antagonist yohimbine increased food intake. Propranolol, apomorphine, haloperidol, 5-HT and methysergide were ineffective.;Vigorous feeding followed injection of morphine into the VMH but injection into lateral, ventral and caudal sites caused less or no ingestion.
Tepperman, Fern Sheila, "Effects Of Opiates And Opioid Peptides In The Hypothalamus On Feeding And Temperature In The Rat" (1983). Digitized Theses. 1286.