An orexigenic role for μ-opioid receptors in the lateral parabrachial nucleus

Abstract

. The pontine parabrachial nucleus (PBN) has been implicated in regulating ingestion and contains opioids that promote feeding elsewhere in the brain. We tested the actions of the selective -opioid receptor (-OR) agonist [D-Ala 2 ,N-Me-Phe 4 ,Gly 5 -ol]enkephalin (DAMGO) in the PBN on feeding in male rats with free access to food. Infusing DAMGO (0.5-4.0 nmol/0.5 l) into the lateral parabrachial region (LPBN) increased food intake. The hyperphagic effect was anatomically specific to infusions within the LPBN, dose and time related, and selective for ingestion of chow compared with (nonnutritive) kaolin. The nonselective opioid antagonist naloxone (0.1-10.0 nmol intra-PBN) antagonized DAMGO-induced feeding, with complete blockade by 1.0 nmol and no effect on baseline. The highly selective -opioid antagonist D-Phe-Cys-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP; 1.0 nmol) also prevented this action of DAMGO, but the -antagonist nor-binaltorphimine did not. Naloxone and CTAP (10.0 nmol) decreased intake during scheduled feeding. Thus stimulating -ORs in the LPBN increases feeding, whereas antagonizing these sites inhibits feeding. Together, our results implicate -ORs in the LPBN in the normal regulation of food intake.feeding; hyperphagia; DAMGO; naloxone; CTAP STIMULATING ANY OF THE SUBTYPES of opioid receptors (ORs; , , ␦) or the related orphan receptor for nociceptin increases food intake in mammals (6,24,26,71,77). The orexigenic effects of these treatments are evident particularly in settings using preferred foods for the test diet (e.g., 39, 94, 95), although consumption of standard chow is also enhanced (9, 72). Conversely, drugs that block ORs reduce food intake (11,16,41,49). This hypophagia may occur especially under conditions when opioid pathways are highly activated (53). The data, therefore, suggest that opioid peptides play roles in the physiological control of feeding.The anatomic loci subserving opioidergic feeding are distributed widely throughout the brain. Attention has focused on the nucleus accumbens (NAC) and the rest of the ventral striatum as a critical region (9,72,94,95). Infusing opioid agonists into the ventral tegmental area of the midbrain, which projects onto the ventral striatum, also stimulates feeding (45, 67); this circuitry is consistent with the view assigning a broader role for opioids to support positive affect and appetitive reward (39, 70). Another (probably integrated) circuit is defined by observations that opioid stimulation of the paraventricular hypothalamic nucleus (21, 22) The parabrachial nucleus (PBN) of the pons has bidirectional communication with the PVN, central nucleus of the amygdala, and NTS (19,29,61,62). The multiple subnuclei of the PBN sort afferent input from second-order sensory neurons originating in the NTS and spinal cord (38,83) and distribute the information to rostral targets (19,36,37,68). This sensory processing includes neurotransmission underlying gustatory and visceral function and their convergence (8,30,38).It is logical, then, that the PBN has been imp...

μ-Opioid modulation in the rostral solitary nucleus and reticular formation alters taste reactivity: evidence for a suppressive effect on consummatory behavior

“…Our results demonstrating that Damgo in the rNST/RF suppresses ingestion contrast with previous work showing that systemic and forebrain injections of MOR ligands facilitate positive taste reactivity responses and intake (2,3,32,37,43,53,74,75). They also seem at odds with the facilitatory effects on feeding when Damgo is injected into the parabrachial nucleus (73). In fact, a series of experiments examining the consequences of manipulating MORs in the vicinity of the rNST likewise suggest that -opioids in the medulla can increase food intake (16,35,36).…”

“…Damgo infused into the pontine parabrachial nucleus (73) facilitates intake of standard chow, whereas an irreversible MOR antagonist attenuates feeding (71). MOR modulation of ingestive behavior also seems likely at the level of the medulla; in particular, in the first gustatory relay, the rostral nucleus of the solitary tract (rNST), and the adjacent parvocellular and intermediate zones of the reticular formation (RF).…”

Central lipid detection and the regulation of feeding behavior

“…There are also found in neural pathways thought to relay taste information (Nucleus Tractus Solitarius (NTS), the parabrachial nucleus (PB) and the AG) (Mansour et al, 1987;Xia and Haddad, 1991). Opioid receptor agonist enhance food intake by increasing the hedonic valence of food (Kotz et al, 1997;Echo et al, 2002;Wilson et al, 2003;Levine et al, 2004;Kelley et al, 2005). Local injection of the selective m-opioid receptor agonist DAMGO into the nucleus accumbens results in increased intake of both fat and carbohydrate-rich diets when either are presented alone (Zhang and Kelley, 1997;Zhang et al, 1998).…”

Chronic prevention of μ-opioid receptor (MOR) G-protein coupling in the pontine parabrachial nucleus persistently decreases consumption of standard but not palatable food

“…Previously, our laboratory demonstrated that acute infusion of the selective μ-opioid receptor (MOR) agonist [D-Ala 2 , N-Me-Phe 4 , Glycinol 5 ]-Enkephalin (DAMGO) into the LPBN increased consumption of standard chow during a 4-h test, and this intake was blocked by pretreatment with the selective and reversible MOR antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH 2 (CTAP) Wilson et al 2003). However, we did not assess the anatomical regions affected by the drug, whether persistent ingestive changes would occur with long-term impairment of receptor function or the degree of inhibition of receptors.…”