Differential Effect of Fixed Ratio Magnitude on the Rate of Lever-Pressing and Interinjection Intervals of Cocaine Self-Administration in Rats.
Differential Effect of Fixed Ratio Magnitude on the Rate of Lever-Pressing and Interinjection Intervals of Cocaine Self-Administration in Rats.
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DOI：
10.1016/j.curtheres.2023.100727
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发表时间：
2023
影响因子：
1.9
通讯作者：
Norman, Andrew B.
中科院分区：
文献类型：
--
作者：
Desai, Jhanvi N.;Muccilli, Abigail R.;Esqueda, Luis E. Tron;Welge, Jeffrey A.;Norman, Andrew B.
自我管理行为的许多特征可以通过参考强化时间表的特性来解释。时间表改变了行为被强化的可能性，从而增加或减少了行为的频率，据报道，固定比率（FR）幅度改变了对可卡因的反应率。药代动力学/药效相互作用理论指出，只有当体内可卡因水平高于启动/缓解阈值且低于饱腹感阈值（称为强迫区的范围）时，才会诱发杠杆按压行为。该理论成功地解释了大鼠可卡因按渐进比例和 FR1 时间表的自我给药。确定高 FR 幅度对可卡因自我给药率和当可卡因水平处于强迫区域内时杠杆按压行为率的影响。大鼠按照 FR1 时间表进行可卡因自我给药，然后切换到从 FR1 开始，然后是 FR 5、10、20 或 50 的疗程。每周在 FR1/FR50 疗程之间仅进行 FR1 疗程，然后仅进行 FR1 疗程数周。 FR1 和 FR50 中单位剂量 3 µmol/kg 的注射间隔是规则的，但完成 50 次按压所需的时间更长。当大鼠在可卡因呈现的 FR50 时间表下维持反应时，与基线 FR1 会话相比，在终止获取可卡因后观察到杠杆按压次数急剧增加，这是先前未报告的发现。然而，只有当可卡因水平处于强迫区时，才会发生杠杆按下，并且这个持续时间没有变化。杠杆按压的增加持续了数周。暴露于 FR50 后，FR1 的注射间隔没有改变。尽管之前被认为是理解可卡因自我给药行为调节的关键，但 FR 幅度只是将注射间隔增加了完成 50 次杠杆按压所需的时间。按下杠杆率的急剧增加是由高 FR 时间表引起的，而不是由可卡因引起的。时间表引起的杠杆按下率增加的效用尚不清楚。强迫区理论为理解可卡因自我给药行为提供了合理的药理学基础。
Many features of self-administration behavior may be explained by reference to the properties of schedules of reinforcement. Schedules alter the probability of a behavior being reinforced and thereby increase, or decrease, the frequency of the behavior and fixed ratio (FR) magnitude reportedly alters the rate of responding to cocaine. A pharmacokinetic/pharmacodynamic interaction theory states that lever-pressing behavior is induced only when cocaine levels in the body are above the priming/remission threshold and below the satiety threshold—a range termed the compulsion zone. This theory successfully explains cocaine self-administration in rats on a progressive ratio and the FR1 schedule. To determine the effects of high FR magnitude on the rate of self-administration of cocaine and the rate of lever-pressing behavior when cocaine levels are within the compulsion zone. Rats acquired cocaine self-administration on an FR1 schedule and then were switched to sessions that started with FR1 and then FR 5, 10, 20, or 50. An only FR1 session was run each week between FR1/FR50 sessions and then only FR1 sessions were conducted for several weeks. Interinjection intervals at a unit dose of 3 µmol/kg were regular at both FR1 and FR50 but were longer by the time required to complete the 50 presses. When responding by rats was maintained under an FR50 schedule of cocaine presentations, compared to baseline FR1 sessions, dramatic increases in the number of lever-presses were observed after access to cocaine was terminated, a previously unreported finding. However, lever-pressing occurred only when cocaine levels were in the compulsion zone, and this duration was unchanged. The increase in lever-pressing persisted for weeks. Interinjection intervals at FR1 were not altered after exposure to FR50. Although previously considered key to understanding the regulation of cocaine self-administration behavior, FR magnitude simply increased interinjection intervals by the time required to complete 50 lever-presses. The dramatic increase in the rate of lever-pressing was caused by the high FR schedule rather than cocaine. The utility of the schedule-induced increase in the rate of lever-pressing is unclear. The compulsion zone theory provides a rational pharmacological basis for understanding cocaine self-administration behavior.
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