A naloxonazine sensitive (μ1 receptor) mechanism in the parabrachial nucleus modulates eating

Abstract

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 µ opioid receptors (MOPR) in the lateral PBN increased food consumption. MOPR's have been divided operationally into µ 1 and µ 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 µ 1 /µ 2 agonist DAMGO (D-Ala2, N-Me-Phe4, Gly5-ol-enkephalin) of the incorporation of [ 35 S]-guanosine 5'(γ-thio)triphosphate ([ 35 S]-GTPγS) into sections of the PBN. In vitro, Nlxz dose dependently inhibited receptor coupling in all areas of the PBN. The 1µM 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 24h 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 µ 1 opioid receptor subtype is present in the parabrachial nucleus of the pons and that these receptors serve to modulate feeding in rats.

Loss of GABAergic Signaling by AgRP Neurons to the Parabrachial Nucleus Leads to Starvation

“…The PBN is the most responsive brain region where benzodiazepine injection promotes taste reactivity (Berridge and Pecina, 1995). Direct injections of cannabinoid or mu-opioid receptor agonists into the PBN stimulate feeding (Chaijale et al, 2008;DiPatrizio and Simansky, 2008;Wilson et al, 2003). Thus, the PBN can process both aversive and appetitive ascending visceral information to modulate feeding behavior.…”

Estradiol interacts with an opioidergic network to achieve rapid modulation of a vocal pattern generator

“…Therefore, suppression was common to all three antagonists as was a rapid recovery to baseline. Relative to the other antagonists, the naloxone effect was delayed but similarly short-lived, which may relate to differences in the ability of each drug to penetrate neural tissue due to chemical structure or potency (see also Martin et al 2006 ; Chaijale et al 2008 ). It is noteworthy that the binding affinity of opioid antagonists to mu- and kappa-opioid receptors have been well-characterized for mammals, but not yet for teleost fishes.…”

Advances in the neurobiological bases for food ‘liking’ versus ‘wanting’

“…For example, work by Simansky and colleagues showed that opioid and endocannabinoid stimulation within parabrachial nucleus also robustly increases consumption of palatable food (Wilson et al, 2003; DiPatrizio and Simansky, 2008). Further, endogenous opioid function within PBN appears to be required for food motivation, as infusions of naloxonazine completely prevented DAMGO induced hyperphagia (Chaijale et al, 2008). …”