Salem A, Hope W
School of Pharmaceutical Biology and Pharmacology, Victorian College of Pharmacy, Monash University, Parkville, Australia.
Pharmacol Biochem Behav. 1997 Aug;57(4):671-9. doi: 10.1016/s0091-3057(96)00393-0.
The effects of the selective A1 adenosine receptor agonist N6-cyclopentyladenosine (CPA) and the selective A2a agonist 2-[p-(2-carboxethyl)phenylethyl-ethylamino]-5'-ethylcarboxamidoade nosine (CGS 21680) (each at 0.03, 0.1 and 0.3 mg/kg, SC) as well as the selective A1 adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), non-selective antagonists 3-isobutyl-1-methylxanthine (IBMX), aminophylline, 3,7-dimethyl-1-propargyl-xanthine (DMPX) and 8(p-sulfophenyl)-theophylline (8-SPT) were investigated (each at 5, 10 and 30 mg/kg, SC) for their ability to alter the naloxone-precipitated opiate withdrawal syndrome in morphine-dependent rats. Effects of CPA and CGS 21680 on opiate withdrawal in the presence of aminophylline were also investigated. Both CPA and CGS 21680, caused a significant reduction in the incidence of body shakes, teeth chatter and paw shakes and decreased the amount of faecal matter produced. DPCPX, IBMX, DMPX, 8-SPT and aminophylline significantly increased the incidence of jumps and decreased the amount of faecal matter produced. The incidence of body shakes was significantly increased by DMPX, 8-SPT and IBMX. Neither CPA nor CGS 21680 were able to reverse the significant increase in the incidence of jumps caused by aminophylline. These data suggest that there is a role for endogenous adenosine in the modulation of the opiate abstinence syndrome and both A1 and A2a adenosine receptors are involved in this phenomenon.
研究了选择性A1腺苷受体激动剂N6-环戊基腺苷（CPA）和选择性A2a激动剂2-[对-(2-羧乙基)苯乙基-乙氨基]-5'-乙基羧酰胺基腺苷（CGS 21680）（均为0.03、0.1和0.3mg/kg，皮下注射）以及选择性A1腺苷受体拮抗剂8-环戊基-1,3-二丙基黄嘌呤（DPCPX）、非选择性拮抗剂3-异丁基-1-甲基黄嘌呤（IBMX）、氨茶碱、3,7-二甲基-1-丙炔基黄嘌呤（DMPX）和8-(对-磺基苯基)茶碱（8-SPT）（均为5、10和30mg/kg，皮下注射）改变吗啡依赖大鼠中纳洛酮诱发的阿片戒断综合征的能力。还研究了CPA和CGS 21680在氨茶碱存在下对阿片戒断的影响。CPA和CGS 21680均显著降低了身体抖动、牙齿打颤和爪子抖动的发生率，并减少了粪便产生量。DPCPX、IBMX、DMPX、8-SPT和氨茶碱显著增加了跳跃的发生率，并减少了粪便产生量。DMPX、8-SPT和IBMX显著增加了身体抖动的发生率。CPA和CGS 21680均无法逆转氨茶碱引起的跳跃发生率的显著增加。这些数据表明内源性腺苷在阿片戒断综合征的调节中起作用，并且A1和A2a腺苷受体均参与了这一现象。
