. 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...

Acute pharmacological studies have implicated mu-opioid receptors (MORs) in the shell of the nucleus accumbens (NAC) in mediating responses for palatable food and other natural and drug-induced rewards. However, the long-term behavioral effects of inactivating signal transduction via accumbal MORs, as quantified by an anatomically defined loss of cellular activity, have never been analysed. We combined microinfusion of the irreversible MOR antagonist, beta-funaltrexamine (beta-FNA; 8.0 nmol/0.8 microL, n=9; controls, n=6) with mapping by [35S]GTPgammaS autoradiography to demonstrate an anatomically specific loss of the coupling of MORs to their G-proteins in the dorsal caudomedial shell of the NAC in rabbits. beta-FNA did not alter the stimulated coupling of kappa-opioid receptors. This selective blockade of the cellular function of MORs persistently decreased consumption of a palatable sucrose solution by 40% during a daily 4-h test conducted 2, 3 and 4 days after infusion. beta-FNA did not alter body weight or 20-h consumption of standard chow or water. In 10 different rabbits, infusion of the selective, competitive MOR antagonist, CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2) into the same locus produced a reversible decrease in sucrose consumption, with normal intakes returning on the next day. Together, these data appear to establish that MORs in this accumbal subregion support responding for orosensory reward. Overall, these results visualize a discrete brain locus where cellular actions of endogenous opioids mediate behaviors involved in self-administration of foods and perhaps other hedonically valued substances, such as ethanol and drugs of abuse.

Neurons that synthesize the morphine modulatory peptide neuropeptide FF (NPFF; Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2) densely innervate the parabrachial nucleus (PBN), an area implicated in regulating food intake. We analyzed opioid-related actions of NPFF in feeding in adult male Sprague-Dawley rats. Unilateral infusion of 2 nmol/0.5 microl of the mu-opioid receptor agonist [d-Ala2,NMe-Phe4,glycinol5]enkephalin (DAMGO) into the lateral PBN increased 4-h food intake from 0.7 +/- 0.1 to 3.3 +/- 0.3 g. NPFF (1.25-5.0 nmol) prevented this hyperphagic mu-opioidergic action. In rats fed after 4-h deprivation (baseline = 12.3 +/- 0.3 g/2 h), 5 nmol of NPFF did not alter and larger doses (10 and 20 nmol) actually increased food intake (+36, 54%). Twenty nanomoles also elevated intake of freely feeding rats (from 0.7 +/- 0.1 to 5.1 +/- 1.0 g/4 h). The opioid receptor blocker naloxone (10 nmol) antagonized this increase. These data reveal both pro- and anti-opioid actions of NPFF in the PBN to modulate feeding. The mechanisms for the opposite actions of low and high concentrations of this neuropeptide in parabrachial regulation of food intake remain to be determined.

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