Effects of endogenous opioid peptides and their analogs on the activities of hypothalamic arcuate neurons in brain slices from diestrous and ovariectomized rats

Abstract

Various endogenous opioid peptides and some of their analogs were used in this study to test their effects on the membrane activities of hypothalamic arcuate neurons in brain slices. Both ovariectomized and diestrous rats were used in the study, and freshly prepared brain slices from these animals were used for extracellular single-unit recording studies. All of the opioids exhibited potent inhibitory effects on the firing of arcuate neurons, viz., β-endorphin inhibited 55% ( n = 33), DAGO 62% ( n = 21), dynorphin A 55% ( n = 11), U50,488 36% ( n = 39), Met-enkephalin 35% ( n = 54), and DPDPE 50% ( n = 8) of tested arcuate neurons from ovariectomized rats. Significantly higher percentage of inhibition was observed in slice preparations from diestrous rats for DAGO 86% ( n = 22), and slightly higher for dynorphin A 59% ( n = 22) and U50,488 53% ( n = 15). Pretreatment with naloxone prevented most of the actions by β-endorphin and DAGO, and nor-binaltorphimine prevented those by dynorphin A and U50,488. Most of the effects of Met-enkephalin could also be blocked by nor-binaltorphimine (67%, n = 6), but less by naltrindole (25%, n = 8). Naltrindole, however, seemed to be more effective in blocking the action of [D-Pen 2,5]-enkephalin (100%, n = 2). In summary, all opioids tested exerted potent inhibitory effects upon the firing of arcuate neurons possibly through multiple opioid receptors, and the presence of ovarian hormones may have an effect on the neuron's responsiveness to opioid acting on μ type receptors.