Abstract
Abstract
Heroin, like morphine, given intracerebroventricularly produces analgesia by acting on μ opioid receptors in most mice. In contrast, in Swiss Webster mice, heroin has the unusual property of acting on brain δ opioid receptors whereas morphine still acts on μ receptors. The literature indicates that in diabetic mice and rats, the μ agonist potency of morphine is diminished while that to a δ receptor agonist is enhanced. The purpose of the present study was to determine if the response to heroin occurred through a δ receptor in the brain of streptozotocin-induced diabetic Sprague-Dawley rats. One week after a cannula was surgically implanted in the lateral ventricle, diabetes was 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 antagonists. In nondiabetic rats, a rightward shift in the dose response curve for heroin was produced by naloxone. D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-ThrNH2, a more μ receptor selective antagonist given in a single dose experiment, also inhibited heroin action. Thus, heroin acted on μ receptors. In diabetic rats, intracerebroventricular naltrindole, but not naloxone nor CTOP, inhibited the heroin response and indicated a δ agonist action for heroin. Inhibition by intrathecal yohimbine of the μ (nondiabetic) and bicuculline of the δ response (diabetic) suggested spinal α2-adrenergic and GABAA receptor mediation, respectively, for the descending systems. In conclusion, the response to heroin was changed from μ in nondiabetic rats to a δ receptor action in diabetic rats. Understanding the basis for this change in receptor selectivity of heroin could provide an important avenue for investigating determinants of opioid receptor function.
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