Tolerance to acute ethanol inhibition of peptide hormone release in the isolated neurohypophysis

Background: Acute ethanol (EtOH) exposure reduces the evoked release of vas opressin (AVP) and oxytocin (OT) from excised neurohypophyses and from diss ociated neurohypophysial terminals of the rat. Methods and Results: Rats placed on a diet that maintained blood levels of 30 mM EtOH for 20 to 30 days developed tolerance to acute EtOH inhibition o f release. In the presence of 10 mM EtOH, high (50 mM) K+-induced release o f AVP from isolated neurohypophysial terminals of EtOH-naive rats was reduc ed by 77.7 +/- 1.4%, whereas in the chronic EtOH group, release was reduced by only 9.4 +/- 8.7%. Similar tolerance was evident during acute challenge with 75 mM EtOH, as well as for release of OT from isolated terminals. Ani mals treated with an intraperitoneal injection of EtOH and sacrificed 90 mi n postinjection did not exhibit the reduced EtOH inhibition of release from dissociated terminals during a 75 mM EtOH acute challenge. Conclusions: The altered component responsible for the tolerance to inhibit ion of release resides in the isolated terminal, because tolerance measured in vitro from intact neurohypophyses was similar to that seen in isolated terminals. The failure of EtOH-injected animals to exhibit reduced inhibiti on of release in response to an acute EtOH challenge indicates that short-t erm elevated blood alcohol level does not induce this tolerance. The findin g of tolerance to EtOH-induced inhibition of release from the intact neuroh ypophysis and isolated terminals provides a physiological preparation in wh ich to examine the molecular targets of acute drug action modified after ch ronic exposure to the drug.