Direct inhibition by opioid peptides of neurones located in the ventromedial nucleus of the guinea pig hypothalamus.

In slices of guinea pig brain, intracellular recordings were obtained from neurones of the ventromedial nucleus of the hypothalamus (VMH). [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAGO), an agonist selective for mu-opioid receptors, caused an inhibition of spontaneous firing activity and a membrane hyperpolarization. This effect was reversible, concentration-dependent and could be blocked by naloxone. DAGO directly inhibited VMH neurones since its effect persisted when the slice was perifused with a solution that blocks synaptic transmission. The hyperpolarization induced by DAGO was associated with a marked decrease in membrane input resistance and it was reversed in polarity at membrane potentials 30-40 mV more negative than the resting potential. A chloride current did not contribute to the hyperpolarization brought about by DAGO. We conclude that DAGO inhibits VMH neurones, probably by opening membrane potassium channels.