Delta and Kappa Opioid Receptor Subtypes and Ingestion: Antagonist and Glucoprivic Effects

Delta and kappa opioid receptors have been differentiated into further subtypes based upon both biochemical and pharmacological analgesic assays. Whereas hyperphagia elicited by the kappa1 receptor agonist, U50488H is blocked by general and kappa1 opioid antagonists, hyperphagia elicited by the kappa3 receptor agonist, naloxone benzoylhydrazone (NalBzOH) is blocked by general, but not kappa1 opioid antagonists. The first study assessed the opioid antagonist profile of hyperphagia elicited by centrally administered delta1 ([D-Pen2, D-Pen5 ]-enkephalin, DPDPE: 5-50 μg) and delta2 ([D-Ala2, Glu4 ]-Deltorphin, Delt II: 5-50 μg) agonists following central pretreatment with general (naltrexone), delta1 ([D-Ala2, Leu5, Cys6 ]-enkephalin, DALCE) and delta2 (naltrindole isothiocyanate, NTII) opioid antagonists. It is also important to determine whether selective opioid receptor subtype agonists are capable of altering intake in ingestive situations other than spontaneous feeding. The second study examined whether centrally administered delta1, delta2, kappa1 or kappa3 agonists altered the pattern and magnitude of hyperphagia elicited by 2-deoxy-d-glucose (2DG: 50-400 mg/kg, IP). DPDPE-induced hyperphagia was significantly reduced by naltrexone and NTII, but not DALCE. Delt II-induced hyperphagia was significantly reduced by DALCE and NTII, but not naltrexone. Pairing Delt II (5 μg) with low (100-200 mg/kg) 2DG doses significantly enhanced intake, producing a leftward (3-fold) shift in 2DG's hyperphagic dose-response curve. In contrast, DPDPE failed to alter 2DG-induced hyperphagia, and kappa1 and kappa3 opioid agonists each produced small, but significant increases in 2DG-induced hyperphagia. The antagonist data suggest the possibility of physiological and pharmacological interactions between delta receptor subtypes in mediating food intake, and it would appear that delta2 opioid receptors exert facilitatory effects upon glucoprivic hyperphagia.