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Peptides that Regulate Food Intake

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

Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102

Submitted 4 March 2003 ; accepted in final form 11 August 2003

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 µ-opioid receptor (µ-OR) agonist [D-Ala²,N-Me-Phe⁴,Gly⁵-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 µl) 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 µ-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 µ-ORs in the LPBN increases feeding, whereas antagonizing these sites inhibits feeding. Together, our results implicate µ-ORs in the LPBN in the normal regulation of food intake.

feeding; hyperphagia; DAMGO; naloxone; CTAP

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