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 α 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 δ-opioid antagonist, naltrindole (0.1, 1 mg/kg, i.p.) nor by the μ/δ-antagonist, RX8008M (16-methyl cyprenorphine; 0.1, 1 mg/kg, i.p.), which clearly discriminates between μ/δ- and k- 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 k , as opposed to μ or δ-opioid receptors. This response is unlikely to be due to α 2-adrenoceptor blockade, since other highly selective α 2-adrenoceptor antagonists do not increase food intake and, instead may reflect the high affinity of idazoxan for non-adrenoceptor idazoxan binding sites.