HEROIN ACTS ON DELTA-OPIOID RECEPTORS IN THE BRAIN OF STREPTOZOCIN-INDUCED DIABETIC RATS

Heroin, like morphine, given intracerebroventricularly produces analge sia by acting on mu opioid receptors in most mice. In contrast, in Swi ss Webster mice, heroin has the unusual property of acting on brain de lta opioid receptors whereas morphine still acts on CI receptors, The literature indicates that in diabetic mice and rats, the CI agonist po tency of morphine Is diminished while that to a delta receptor agonist is enhanced. The purpose of the present study was to determine if the response to heroin occurred through a delta receptor in the brain of streptozotocin-induced diabetic Sprague-Dawley rats. One week after a cannula was surgically implanted in the lateral ventricle, diabetes wa s induced by intravenous administration of 55 mg/kg of streptozotocin, Three days later the receptor selectivity of intraventricular heroin in the tail flick test was determined by coadministration of opioid an tagonists. In nondiabetic rats, a rightward shift in the dose response curve for heroin was produced by naloxone. D-Phe-Cys-Tyr-D-Trp-Orn-Th r-Pen-ThrNH(2), a more mu receptor selective antagonist given in a sin gle dose experiment, also inhibited heroin action. Thus, heroin acted on mu receptors, In diabetic rats, intracerebroventricular naltrindole , but not naloxone nor CTOP, inhibited the heroin response and indicat ed a delta agonist action for heroin. Inhibition by intrathecal yohimb ine of the mu (nondiabetic) and bicuculline of the delta response (dia betic) suggested spinal alpha(2)-adrenergic and GABA(A) receptor media tion, respectively, for the descending systems. In conclusion, the res ponse to heroin was changed from mu in nondiabetic rats to a delta rec eptor action in diabetic rats. Understanding the basis for this change in receptor selectivity of heroin could provide an important avenue f or investigating determinants of opioid receptor function.