A naloxonazine sensitive (mu1 receptor) mechanism in the parabrachial nucleus modulates eating

The parabrachial nucleus (PBN) is an area of the brain stem that controls eating and contains endogenous opioids and their receptors. Previously, we demonstrated that acute activation of mu opioid receptors (MOPR) in the lateral PBN increased food consumption. MOPRs have been divided operationally into mu(1) and mu(2) receptor subtypes on the basis of the ability of naloxonazine (Nlxz) to block the former but not the latter. We used autoradiography to measure whether Nlxz blocks stimulation by the mu(1)/mu(2) agonist DAMGO (D-Ala2, N-Me-Phe4, Gly5-ol-enkephalin) of the incorporation of [(35)S]-guanosine 5'(gamma-thio)triphosphate ([(35)S]-GTPgammaS) into sections of the PBN. In vitro, Nlxz dose dependently inhibited receptor coupling in all areas of the PBN. The 1 muM concentration of Nlxz reduced stimulation by 93.1+/-5% in the lateral inferior PBN (LPBNi) and by 90.5+/-4% in the medial parabrachial subregion (MPBN). Administration of Nlxz directly into the LPBNi decreased both food intake and agonist stimulated coupling, ex vivo, for the 24-h period after infusion. Infusion of Nlxz into the intended area reduced food intake by 42.3% below baseline values. Nlxz infusion prevented DAMGO stimulation of G-protein coupling in LPBNi and markedly reduced this stimulation in the MPBN. The incomplete inhibition of DAMGO-stimulated coupling in the MPBN is most likely due to the limited diffusion of Nlxz from the site of infusion (LPBNi) into this brain region. In conclusion, this study demonstrates that the mu(1) opioid receptor subtype is present in the parabrachial nucleus of the pons and that these receptors serve to modulate feeding in rats.