Functional analysis of opioid receptor subtypes in the ventromedial hypothalamic nucleus of the rat

Effects of [Met5]enkephalin and agonists selective for mu-, delta- and kappa-opioid receptors were tested in vitro on neurons of the hypothalamic ventromedial nucleus of ovariectomized, estrogen-primed rats. Brain slices were perfused with artificial cerebrospinal fluid and opioid drugs were applied by bolus injection into the perfusion line. Single unit activity was recorded extracellularly. The majority of ventromedial hypothalamic nucleus neurons tested exhibited marked inhibitory responses to [Met5]enkephalin. The inhibition was blocked by naloxone, by the selective delta-opioid receptor antagonist naltrindole and, to a lesser extent, by the mu-opioid receptor antagonist beta-funaltrexamine. The kappa-opioid receptor antagonist nor-binalmorphimine had virtually no effect on [Met5]enkephalin inhibition. Agonists selective for delta-([D-Pen2,D-Pen5]enkephalin, DPDPE) and for mu-([D-Ala2,MePhe4,Gly-ol5]enkephalin, DAGO) opioid receptors also potently inhibited the ventromedial hypothalamic nucleus neurons while the kappa-opioid receptors agonist U50,488 only produced a small inhibition in a smaller number of units. These results provide functional evidence that [Met5]enkephalin, a potential opioid transmitter in the ventromedial hypothalamic nucleus, can exert an inhibitory effect by acting on delta-and mu-opioid receptors.