Bertalmio A J, Woods J H
Department of Psychology, University of Michigan, Ann Arbor 48109-0626.
J Pharmacol Exp Ther. 1989 Nov;251(2):455-60.
Apparent pA2 analysis was used to determine whether the short-duration opioid agonist, alfentanil, acts at mu receptors in the positive reinforcement of operant behavior in the rhesus monkey. In test sessions a red light signaled the availability of alfentanil injections. If a monkey pressed a response lever 30 times, a specific dose of alfentanil was injected i.v., and the red light was extinguished for 10 min. This cycle could be repeated for up to 130 min, the maximum length of a session. Between successive test sessions at least three maintenance sessions were held; in these sessions injections of 0.32 mg/kg/injection of codeine were made available. The dose of alfentanil was changed from one test session to the next, and dose-dependent changes in rates of responding resulted. Rates reached 3.05 responses/sec at 0.010 mg/kg/injection, the highest dose tested. The opioid antagonist, quadazocine, produced dose-dependent, parallel shifts to the right in the alfentanil dose-response curve. In Schild Plot analysis the regression line fit to the antagonism data had a slope of -1.1; the apparent pA2 value for quadazocine was 7.6. This value was close to apparent pA2 values obtained with mu agonists in studies of other behavioral effects of opioids, but distinct from values obtained with kappa agonists in those studies. Thus, it is likely that mu receptors mediate the positive reinforcing effect of alfentanil.
采用表观pA2分析来确定短效阿片类激动剂阿芬太尼是否通过作用于μ受体来强化恒河猴操作性行为中的阳性强化作用。在测试阶段，红灯亮起表示可注射阿芬太尼。如果猴子按压反应杆30次，就静脉注射特定剂量的阿芬太尼，红灯熄灭10分钟。这个循环最多可重复130分钟，即一次测试的最长时长。在连续的测试阶段之间至少进行三次维持阶段测试；在这些阶段，可注射0.32mg/kg/次的可待因。阿芬太尼的剂量在不同测试阶段会有所变化，由此产生了反应率的剂量依赖性变化。在测试的最高剂量0.010mg/kg/次时，反应率达到3.05次/秒。阿片类拮抗剂夸达佐辛使阿芬太尼剂量-反应曲线呈剂量依赖性、平行向右移动。在Schild图分析中，拟合拮抗数据的回归线斜率为-1.1；夸达佐辛的表观pA2值为7.6。该值与在阿片类药物其他行为效应研究中使用μ激动剂获得的表观pA2值相近，但与使用κ激动剂在这些研究中获得的值不同。因此，μ受体很可能介导了阿芬太尼的阳性强化作用。
