Griffiths R R, Bradford L D, Brady J V
Psychopharmacology (Berl). 1979 Oct;65(2):125-36. doi: 10.1007/BF00433038.
Responding maintained under progressive ratio (PR) and fixed ratio (FR 160) schedules of IV saline or cocaine (0.01-4.0 mg/kg) injections was studied in baboons. Each injection was followed by a time-out period which was 3-h with the PR schedule and was either 3 or 12 with the FR schedule. On the PR schedule the ratio requirement was systematically increased each day until reaching the 'breaking point' at which self-injection performance fell below a criterion level (one or zero injections per day). Overall response rates on the PR schedule increased with progressive increases in the ratio until a maximum at which an abrupt reduction in responding occurred. With the 3-h time-out the dose-breaking point function on the PR schedule was similar to the dose-response rate function on the FR schedule. These dose-effect functions were inverted U-shaped curves characterized by a graded ascending limb (0.01-0.32 mg/kg) and a downturn at the highest doses (3.0-4.0 mg/kg). On the FR schedule the downturn in the dose-response rate function was attributable to a cumulative drug effect as revealed by manipulation of time-out duration and analysis of sequential interresponse time distributions and cumulative response records. PR and FR schedules provide similar information about the relative reinforcing efficacy of different cocaine doses.
在狒狒身上研究了静脉注射生理盐水或可卡因(0.01 - 4.0毫克/千克)时,在累进比率(PR)和固定比率(FR 160)给药方案下反应的维持情况。每次注射后有一个超时阶段,PR给药方案下为3小时,FR给药方案下为3小时或12小时。在PR给药方案中,比率要求每天系统地增加,直到达到“突破点”,此时自我注射行为降至标准水平以下(每天一次或零次注射)。PR给药方案下的总体反应率随着比率的逐步增加而增加,直至达到最大值,此时反应突然减少。在3小时的超时情况下,PR给药方案下的剂量 - 突破点函数与FR给药方案下的剂量 - 反应率函数相似。这些剂量效应函数呈倒U形曲线,其特征为一个逐渐上升的分支(0.01 - 0.32毫克/千克)以及在最高剂量(3.0 - 4.0毫克/千克)时的下降趋势。在FR给药方案下,剂量 - 反应率函数的下降归因于累积药物效应,这通过对超时持续时间的操作以及对连续反应间隔时间分布和累积反应记录的分析得以揭示。PR和FR给药方案提供了关于不同可卡因剂量相对强化效力的相似信息。