Endogenous opioid regulation of oxytocin secretion through pregnancy in the rat

We have investigated the influence of endogenous opioids on oxytocin secretion during pregnancy. In blood-sampled conscious rats on days 18 and 21 of pregnancy plasma oxytocin concentration, measured by radioimmunoassay, was significantly increased compared to non-pregnant or post-partum rats. On days 15, 18 and 21 of pregnancy but not in non-pregnant, early pregnant or post-partum rats, the opioid antagonist naloxone caused a significant increase in plasma oxytocin compared to vehicle injection, indicating activation of an endogenous opioid restraint over oxytocin secretion. Electrically stimulated neural lobes isolated from 16- and 21-day pregnant rats released more oxytocin than those from non-pregnant rats. However, naloxone (10(-5) M) was less effective at potentiating, and the kappa-opioid agonist U50,488 (10(-5)M) was less effective at inhibiting, stimulated release at the end of pregnancy than in non-pregnant rats suggesting desensitization of oxytocin nerve terminals to actions of endogenous opioids. Neural lobes from male rats drinking 2% saline for 4 days also showed desensitization of oxytocin nerve endings to naloxone. Neither neural lobe content of dynorphin A(1-8), an endogenous kappa-opioid, nor prodynorphin mRNA expression, measured by in situ hybridization histochemistry in the supraoptic nucleus altered during pregnancy. However, neural lobe content of Met5-enkephalin significantly decreased by day 21 of gestation suggesting enhanced release.(ABSTRACT TRUNCATED AT 250 WORDS)