Coffin V L, Carney J M
Neuropharmacology. 1986 Oct;25(10):1141-7. doi: 10.1016/0028-3908(86)90162-0.
Acute administration of N6(L-phenylisopropyl)adenosine (L-PIA; 0.01-0.178 mg/kg, s.c.), N6-cyclohexyladenosine (CHA; 0.01-0.178 mg/kg, s.c.), 2-chloroadenosine (2-CA; 0.32-0.56 mg/kg, s.c.), N6-cycloheptyladenosine (CHPA; 0.032-1.0 mg/kg, s.c.), N6-phenyladenosine (PA; 0.1-1.0 mg/kg, s.c.), N6(D-phenylisopropyl)adenosine (D-PIA; 0.32-1.0 mg/kg, s.c.) and N6-benzyladenosine (BA; 1.0-17.8 mg/kg, s.c.) produced dose-related decreases in responding under a fixed-ratio (FR) schedule of food reinforcement. Dose-effect curves were determined by administering cumulative doses (s.c.) during periods that preceded the sequential components of the schedule. Neither 2-chloroadenine arabinoside (2-CAB) nor 2',5'-dideoxyadenosine (2',5'-DDA) altered fixed-ratio responding at the doses studied (0.1-3.2 and 1.0 and 3.2, respectively). Caffeine (0.32 and 3.2 mg/kg) antagonized the behavioral effects of L-PIA in a dose-related, surmountable manner. Daily administration of L-PIA (0.1 mg/kg) resulted in the development of tolerance to the effects of L-PIA decreasing rate and cross-tolerance to other analogs of adenosine (CHA, BA, D-PIA). No cross-tolerance was produced to caffeine, levorphanol or chlordiazepoxide. The activity and order of potency of the analogs of adenosine tested were consistent with the effects of agonists at A1 adenosine receptors. Furthermore, the results demonstrate that the behavioral effects of N6- and 2-chlorine-substituted analogs of adenosine probably act through similar CNS mechanism(s).
皮下注射 N6（L-苯异丙基）腺苷（L-PIA；0.01 - 0.178毫克/千克）、N6-环己基腺苷（CHA；0.01 - 0.178毫克/千克）、2-氯腺苷（2-CA；0.32 - 0.56毫克/千克）、N6-环庚基腺苷（CHPA；0.032 - 1.0毫克/千克）、N6-苯腺苷（PA；0.1 - 1.0毫克/千克）、N6（D-苯异丙基）腺苷（D-PIA；0.32 - 1.0毫克/千克）和 N6-苄基腺苷（BA；1.0 - 17.8毫克/千克）后，在食物强化的固定比率（FR）程序下，反应出现剂量相关的减少。剂量效应曲线通过在程序的连续成分之前的时间段内给予累积剂量（皮下注射）来确定。在所研究的剂量下（分别为0.1 - 3.2和1.0以及3.2），2-氯阿拉伯糖苷腺嘌呤（2-CAB）和2'，5'-二脱氧腺苷（2'，5'-DDA）均未改变固定比率反应。咖啡因（0.32和3.2毫克/千克）以剂量相关的、可克服的方式拮抗L-PIA的行为效应。每日注射L-PIA（0.1毫克/千克）导致对L-PIA降低反应率的效应产生耐受性，并对其他腺苷类似物（CHA、BA、D-PIA）产生交叉耐受性。对咖啡因、左啡诺或氯氮卓未产生交叉耐受性。所测试的腺苷类似物的活性和效价顺序与A1腺苷受体激动剂的作用一致。此外，结果表明，腺苷的N6-和2-氯取代类似物的行为效应可能通过相似的中枢神经系统机制起作用。
