Effect of nociceptin/orphanin FQ on food intake in rats that differ in diet preference.

Nociceptin/orphanin FQ (N/OFQ) is an agonist of the ORL1 receptor. Despite homology with opioids, it does not bind to opioid receptors. Recent studies have shown that centrally administered N/OFQ increases food intake in a manner similar to opioid peptides; its effect is naloxone-reversible. Opioids appear to mediate "palatability/reward"-dependent feeding: Opioid agonists increase, while antagonists decrease, the intake of preferred diets. The current project was designed to elucidate whether the effect of N/OFQ on the consumption of preferred foods resembles that of opioid peptides. Rats had a constant access for 2 weeks to two palatable (high sucrose and high fat) diets, and their baseline preferences were established. Based on these preferences, animals were divided into three groups: fat preferrers, sucrose preferrers, and "neutrals". On the experimental day, rats received an intracerebroventricular injection of N/OFQ. Intriguingly, in fat-preferring rats, N/OFQ stimulated the intake of each of the two diets. It had no effect, however, on the consumption of either diet or cumulative food intake in sucrose-preferring or "neutral" animals. Our results reveal that N/OFQ, unlike opioids, does not increase the intake of preferred diets. Thus, it does not seem to mediate "palatability/reward"-driven feeding. Noteworthy, N/OFQ appears to cause hyperphagia only in fat-preferring rats.