Abstract:
A single non-contingent dose of cocaine reinstates extinguished lever pressing behavior in rats trained to self-administer cocaine. This represents a model of relapse in cocaine use disorder and the number of lever presses has been the standard measure. Lever pressing behavior during self-administration occurs only when cocaine levels are below the satiety threshold and above the remission/priming threshold, a range termed the compulsion zone. Calculated cocaine levels at the time of each lever press during an FR1 self-administration session and following a single non-contingent dose of cocaine were compared. The mean latency to lever pressing behavior was dose dependent and ranged from 1 to 11 min after cocaine doses of 2 or 12 μmol/kg, respectively. This is consistent with higher cocaine doses producing levels above satiety threshold that take more time to fall back to that threshold. The level of cocaine when lever pressing occurred was similar whether cocaine was self-administered or after a single dose of cocaine. The number of lever presses after a single cocaine dose was variable and poorly dose dependent. The latency to the start of lever pressing behavior is a more reliable dependent measure than the number of lever presses. In addition, lever pressing behavior occurs only when cocaine levels are within the compulsion zone. The compulsion zone theory not only explains maintained cocaine self-administration behavior, but also explains the reinstatement of lever pressing behavior in response to a single non-contingent cocaine dose.
摘要:
单次非偶然剂量的可卡因可恢复受过训练以自我施用可卡因的大鼠的熄灭杠杆按压行为。这代表了可卡因使用障碍的复发模型,而杠杆按压的次数一直是标准衡量标准。只有当可卡因水平低于饱腹感阈值且高于缓解/启动阈值时,自我给药期间的杠杆压迫行为才会发生,称为强制区的范围。比较了在FR1自我给药期间和单次非偶然剂量可卡因后每次按压杠杆时计算的可卡因水平。杠杆压迫行为的平均潜伏期是剂量依赖性的,在可卡因剂量为2或12μmol/kg后1至11分钟,分别。这与产生高于饱腹感阈值的较高可卡因剂量是一致的,后者需要更多的时间才能回落到该阈值。无论可卡因是自行服用还是单剂量可卡因后,杠杆按压时可卡因的水平都相似。单次可卡因剂量后的杠杆按压次数是可变的,并且剂量依赖性差。与杠杆按压次数相比,开始杠杆按压行为的延迟是更可靠的相关度量。此外,只有当可卡因水平在强制区域内时,才会发生杠杆按压行为。强迫区理论不仅解释了可卡因的自我给药行为,但也解释了响应单一非偶然可卡因剂量的杠杆按压行为的恢复。