Effects of a delta opioid receptor agonist and inhibitors of enkephalin catabolism on periaqueductal gray neurons in the rat midbrain: Anin vitro study

Effects of a selective agonist of delta-opioid receptors, BUBU, and mixed inhibitors of enkephalin-degrading enzymes, RB-38A and RB-101, on the background and evoked activity of periaqueductal gray (PAG) neurons were studied on slices of the rat midbrain. The tested drugs could either activate or depress spontaneously active neurons, or exert no influence on these units, “Silent” neurons generated no responses to application of the above compounds. In 80.5% of the studied neurons, 1 μM BUBU evoked depression, while 6.5 μM RB-38A, 0.65 mM RB-38A, and 10 μM RB-101 depressed 68.8%, 73.7% and 68.8% of the neurons, respectively. Facilitatory effects were induced by the above drugs in 5.0%, 5.9%, 15.8%, and 6.2% of the cells under study, respectively. The effects of RB-38A and RB-101 differed from the BUBU-evoked responses in a shorter latency and rise time and a higher intensity. Repeated application of RB-38A provided no significant changes in the duration and intensity of the inhibitory effects. Co-administration of RB-38A and BUBU, or BUBU and RB-38A intensified suppression of the neuronal discharges without considerable changing their duration. It is concluded that administration of inhibitors of enkephalin-degrading enzymes toin vitro midbrain preparations creates a pharmacologically effective level of endogenous enkephalins, which exerts specific inhibitory influence on spontaneously active PAG neurons. The data are in agreement with the supposition on the existence of tonic release of enkephalins in midbrain slice preparations.