Endogenous opioids may be involved in idazoxan-induced food intake.
In this study it has been shown that the unexpected increase in food consumption, produced by the alpha 2-adrenoceptor antagonist idazoxan (10 mg/kg, i.p.) in rats, was significantly attenuated by small doses of the opioid antagonist (-)-naloxone (0.1, 1 mg/kg, i.p.) and totally inhibited by a small dose of naltrexone (1 mg/kg, i.p.). On the other hand, idazoxan-induced feeding was not affected by (+)-naloxone (0.1, 1 mg/kg, i.p.), which is inactive at opioid receptors. In addition, idazoxan-induced food consumption was not blocked by the delta-opioid antagonist, naltrindole (0.1, 1 mg/kg, i.p.) nor by the mu/delta-antagonist, RX8008M (16-methyl cyprenorphine; 0.1, 1 mg/kg, i.p.), which clearly discriminates between mu/delta- and kappa-opioid receptor function in vivo. These findings suggest that idazoxan may lead to the release of endogenous opioid peptides, which subsequently stimulate feeding by activation of kappa-, as opposed to mu- or delta-opioid receptors. This response is unlikely to be due to alpha 2-adrenoceptor blockade, since other highly selective alpha 2-adrenoceptor antagonists do not increase food intake and, instead may reflect the high affinity of idazoxan for non-adrenoceptor idazoxan binding sites.
Reckitt and Colman Psychopharmacology Unit, Department of Pharmacology, School of Medical Sciences, Bristol, U.K.
H C
HC
Jackson
I J
IJ
Griffin
D J
DJ
Nutt
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D004146:Dioxanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D004723:Endorphins / Q000502:physiology*; D019329:Idazoxan; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009019:Morphinans / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology / Q000031:analogs & derivatives; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D004723:Endorphins; D007211:Indoles; D009019:Morphinans; D009292:Narcotic Antagonists; D009270:Naloxone; C051207:16-methylcyprenorphine; D009271:Naltrexone; C055382:naltrindole; D019329:Idazoxan