Spencer D G, Caldwell P, Emmett-Oglesby M W
Neuropharmacology. 1984 Jun;23(6):671-6. doi: 10.1016/0028-3908(84)90149-7.
The contribution of behavioral mechanisms to tolerance to N6-(L-phenylisopropyl)adenosine (L-PIA) was studied, along with the degree of cross-tolerance to other drugs active in the CNS. Rats were stabilized on a fixed-ratio of a 20 lever-pressing schedule for food reward and were then assigned to three daily-treatment groups. One group (saline-behavior associated) was injected with saline 15 min before the session, another (L-PIA-behavior associated) was injected with L-PIA (0.08 mg/kg) 15 min before the session and the last (L-PIA-behavior dissociated) was injected with L-PIA (0.08 mg/kg) immediately after the session. Tolerance developed to the decreasing effects of L-PIA on response rate in both groups, L-PIA-behavior associated and L-PIA-behavior dissociated. Behavioral mechanisms were thus not important in tolerance to L-PIA. In subsequent cross-tolerance tests, L-PIA-tolerant rats were cross-tolerant to the adenosine Al receptor agonist, N6-cyclohexyladenosine. The drugs 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), diazepam, pentobarbital, ketamine, clonidine, d-amphetamine and caffeine did not produce differential effects in L-PIA-tolerant and non-tolerant subjects; however, L-PIA-tolerant subjects were more sensitive to the suppressive effects of chlorpromazine on the response-rate.
研究了行为机制对N6-（L-苯异丙基）腺苷（L-PIA）耐受性的贡献，以及对中枢神经系统中其他活性药物的交叉耐受程度。大鼠在以固定比例的20次杠杆按压时间表获取食物奖励的过程中达到稳定状态，然后被分为三个每日治疗组。一组（盐水-行为关联组）在实验前15分钟注射盐水，另一组（L-PIA-行为关联组）在实验前15分钟注射L-PIA（0.08毫克/千克），最后一组（L-PIA-行为解离组）在实验结束后立即注射L-PIA（0.08毫克/千克）。L-PIA-行为关联组和L-PIA-行为解离组对L-PIA降低反应率的作用均产生了耐受性。因此，行为机制对L-PIA的耐受性并不重要。在随后的交叉耐受测试中，对L-PIA耐受的大鼠对腺苷A1受体激动剂N6-环己基腺苷具有交叉耐受性。4,5,6,7-四氢异恶唑并[5,4-c]吡啶-3-醇（THIP）、地西泮、戊巴比妥、氯胺酮、可乐定、d-苯丙胺和咖啡因在L-PIA耐受和非耐受的实验对象中未产生差异效应；然而，L-PIA耐受的实验对象对氯丙嗪对反应率的抑制作用更为敏感。
