Reciprocal opioid-opioid interactions between the ventral tegmental area and nucleus accumbens regions in mediating μ agonist-induced feeding in rats

Feeding elicited by the μ-selective agonist, [d-Ala², M-Phe⁴, Gly-ol⁵]-encephalin administered into the nucleus accumbens is blocked by accumbal pre-treatment with μ, δ₁, δ₂ and κ, but not μ₁ opioid antagonists. Correspondingly, μ-agonist-induced feeding elicited from the ventral tegmental area is blocked by ventral tegmental area pre-treatment with μ and κ, but not δ opioid antagonists. A bi-directional opioid-opioid feeding interaction has been firmly established such that μ-agonist-induced feeding elicited from the ventral tegmental area is blocked by accumbal naltrexone, and that accumbal μ-agonist-induced feeding is blocked by naltrexone pre-treatment in the ventral tegmental area. To determine which opioid receptor subtypes mediate the regional bi-directional opioid-opioid feeding interactions between these two sites, the present study examined the dose-dependent ability of either general (naltrexone), μ (β- funaltrexamine), κ (nor-binaltorphamine) or δ (naltrindole) opioid antagonists administered into one site to block μ-agonist-induced feeding elicited from the other site. General, μ and κ, but not δ opioid receptor antagonist pre-treatment in the ventral tegmental area dose-dependently reduced μ-agonist-induced feeding elicited from the nucleus accumbens. General, μ and δ, and to a lesser degree κ, opioid receptor antagonist pre-treatment in the nucleus accumbens dose-dependently reduced μ-agonist-induced feeding elicited from the ventral tegmental area. Thus, multiple, but different opioid receptor subtypes are involved in mediating opioid-opioid feeding interactions between the nucleus accumbens and ventral tegmental area regions.