FUNCTIONAL-ANALYSIS OF OPIOID RECEPTOR SUBTYPES IN THE VENTROMEDIAL HYPOTHALAMIC NUCLEUS OF THE RAT

Effects of [Met(5)]enkephalin and agonists selective for mu-, delta- a nd kappa-opioid receptors were tested in vitro on neurons of the hypot halamic ventromedial nucleus of ovariectomized, estrogen-primed rats. Brain slices were perfused with artificial cerebrospinal fluid and opi oid drugs were applied by bolus injection into the perfusion line. Sin gle unit activity was recorded extracellularly. The majority of ventro medial hypothalamic nucleus neurons tested exhibited marked inhibitory responses to [Met(5)]enkephalin. The inhibition was blocked by naloxo ne, by the selective delta-opioid receptor antagonist naltrindole and, to a lesser extent, by the mu-opioid receptor antagonist beta-funaltr examine. The kappa-opioid receptor antagonist nor-binalmorphimine had virtually no effect on [Met(5)]enkephalin inhibition. Agonists selecti ve for delta-([D-Pen(2),D-Pen(5)]enkephalin, DPDPE) and for mu-([D-Ala (2),MePhe(4),Gly-ol(5)]enkephalin, DAGO) opioid receptors also potentl y inhibited the ventromedial hypothalamic nucleus neurons while the ka ppa-opioid receptor agonist U50,488 only produced a small inhibition i n a smaller number of units. These results provide functional evidence that [Met(5)]enkephalin, a potential opioid transmitter in the ventro medial hypothalamic nucleus, can exert an inhibitory effect by acting on delta- and mu-opioid receptors.