- 作者: Jodie J. Rady; James M. Fujimoto
- 作者服務機構: Research Service, Clement J. Zablocki Veterans Affaris Medical Center and Medical College of Wisconsin, Milwaukee, Wisc., USA
- 中文摘要: --
- 英文摘要: It is generally thought that the μ receptor actions ofmetabolites, 6-monoacetylmorphine (6MAM) and mor-phine, account for the pharmacological actions of heroin.However, upon intracerebroventricular (i.c.v.) adminis-tration in Swiss Webster mice, heroin and 6MAM act onδ receptors while morphine acts on μ receptors. SwissWebster mice made tolerant to subcutaneous (s.c.) mor-phine by morphine pellet were not cross-tolerant to s.c.heroin (at 20 min in the tail flick test). Now, opioids weregiven in combination, s.c. (6.5 h) and i.c.v. (3h) preced-ing testing the challenging agonist i.c.v. (at 10 min in thetail flick test). The combination (s.c.+ i.c.v.) morphinepretreatment induced tolerance to the μ action of mor-phine but no cross-tolerance to the δ action of heroin,6MAM and DPDPE and explained why morphine pellet-ing did not produce cross-tolerance to s.c. heroin above.Heroin plus heroin produced tolerance to δ agonists butnot to μ agonists. Surprisingly, all combinations of mor-phine with the δ agonists produced tolerance to mor-phine which now acted through δ receptors (inhibited byi.c.v. naltrindole), an unusual change in receptor selectiv-ity for morphine.
- 中文關鍵字: --
- 英文關鍵字: --