Opioid receptor subtypes associated with ventral tegmental facilitation and periaqueductal gray inhibition of feeding

Eating was induced in sated animals by lateral hypothalamic electrical stimulation following central microinjections of mu- (morphine), delta-([D-Pen2,D-Pen5]enkephalin) or kappa-(U-50,488H) receptor agonists, or saline. With stimulation intensity fixed at a moderate level, time to eat 3 45-mg food pellets decreased with increases in stimulation frequency, approaching an asymptote near 7 s at ca. 70 Hz. Ventral tegmental injections (8 but not 0.8 nmol) of each of the 3 drugs reduced the minimum frequency required to produce eating of 3 pellets within 20 s and reduced the frequency at which asymptotic performance was produced; the drugs were equally effective at these doses. Naloxone (2 mg/kg) reversed the effects of each drug; naloxone was slightly more effective against morphine than against DPDPE or U-50,488H. These data suggest that all 3 receptor classes may contribute to the ventral tegmental facilitation of feeding. Periaqueductal gray injections (16 but not 1.6 nmol) of morphine had the opposite effect; they increased the stimulation frequency required to cause eating of 3 pellets in 20 s, and decreased the speed of eating across all stimulation frequencies. Periaqueductal gray injections of the delta- and kappa-agonists were each without effect. These data indicate that the periaqueductal gray inhibition of feeding is mediated solely by mu-receptors and their associated periaqueductal gray circuitry.