Heroin Antinociception Changed From Mu to Delta Receptor in Streptozotocin-Treated Mice

[摘要] References(39)Cited-By(7)CD-1 mice were treated intravenously with streptozotocin, 200 mg/kg, and tested 2 weeks later or treated with 60 mg/kg and tested 3 days later. Both treatments changed the tail flick response of heroin and 6-monoacetylmorphine (6 MAM) given intracerebroventricularly from a μ- to δ-opioid receptor-mediated action as determined by differential effects of opioid receptor antagonists. The response to morphine remained μ. Heroin and 6 MAM responses involved δ1 (inhibited by 7-benzylidenenaltrexone) and δ2 (inhibited by naltriben) receptors, respectively. These δ-agonist actions did not synergize with the μ-agonist action of morphine in the diabetic mice. The expected synergism between the δ agonist, [D-Pen2-D-Pen5]enkephalin (DPDPE), and morphine was not obtained in diabetic mice. Thus, diabetes disrupted the purported μ/δ-coupled response. In nondiabetic CD-1 mice, heroin and 6 MAM produced a different μ-receptor response (not inhibited by naloxonazine) from that of morphine (inhibited by naloxonazine). Also, these μ actions, unlike that of morphine, did not synergize with DPDPE. The unique receptor actions and changes produced by streptozotocin suggest that extrinsic in addition to genetic factors influence the opioid receptor selectivity of heroin and 6 MAM.

[学科分类] 药理学

[关键词] Streptozotocin;Heroin antinociception;μ- and δ-opioid;Receptor selectivity change