Background

Periods of engaging in an alternative behavior diminishes behavioral control by stimuli occasioning alcohol use. This increase in relapse resistance with increasing recovery suggests that changing stimulus control over substance use may be a mechanism responsible for decreased relapse rates with longer recovery. However, the generality of this phenomenon to other drugs of abuse, including opioid self-administration, remains unclear. This study tests the generality of these findings with etonitazene to determine whether the shift in attention represents a behavioral process that generalizes from conditions we previously reported.

Methods

Five adult male Lewis rats were trained to respond on levers under two stimulus conditions; high-cost food (food FR150 and etonitazene FR5) and low-cost food (both food and etonitazene FR 5). Next, only the high-cost food stimulus (occasioning etonitazene responding) was presented for 20 sessions (Use Phase) followed by 9 sessions in which only the low-cost food stimulus (occasioning food responding) was presented (Recovery Phase). During the Recovery Phase, testing occurred during the first component of sessions 0, 1, 2, 4, and 8 when rats were re-exposed to the high-cost food stimulus. The number of food responses prior to completing the etonitazene response requirement during this stimulus exposure was the primary measure.

Results

Food responses during stimulus re-exposure increased significantly as a function of recovery sessions completed with a slope [95 % CI] of 2.49 responses/recovery session [0.16, 4.81]. The average number of etonitazene deliveries per use session was 32 ± 6.6 or an average daily dose of 48.8 ± 10.1 μg/kg. During Recovery Phase, etonitazene deliveries decreased to 2.4 ± 1 or 3.6 ± 1.5 μg/kg.

Conclusion

The decrease in stimulus control observed for ethanol self-administration appears to generalize to opioid self-administration, indicating this change in stimulus control may play a general role in recovery.

中文翻译：

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随着恢复时间的延长，对阿片类药物使用的刺激控制发生变化

背景

一段时间内从事替代行为会减少饮酒刺激造成的行为控制。随着恢复的增加，复发抵抗力的增加表明，改变对物质使用的刺激控制可能是导致复发率随着恢复时间的延长而降低的机制。然而，这种现象对于其他滥用药物（包括阿片类药物自我给药）的普遍性仍不清楚。这项研究用依托硝嗪测试了这些发现的普遍性，以确定注意力的转移是否代表了我们之前报道的情况概括出来的行为过程。

方法

五只成年雄性路易斯大鼠接受训练，在两种刺激条件下对杠杆做出反应；高成本食品（食品 FR150 和依托硝氮 FR5）和低成本食品（食品和依托硝氮 FR 5）。接下来，在 20 个疗程（使用阶段）中仅提供高成本食物刺激（偶尔出现依托尼嗪反应），随后进行 9 个疗程，其中仅出现低成本食物刺激（偶尔出现食物反应）（恢复阶段）。在恢复阶段，测试在第 0、1、2、4 和 8 阶段的第一个部分进行，此时大鼠重新暴露于高成本食物刺激。在该刺激暴露期间完成依托硝嗪反应要求之前的食物反应次数是主要衡量标准。

结果

刺激再次暴露期间的食物反应随着恢复疗程的完成而显着增加，斜率 [95% CI] 为 2.49 反应/恢复疗程 [0.16, 4.81]。每次使用期间的平均依托氮嗪给药次数为 32 ± 6.6 次，或平均每日剂量为 48.8 ± 10.1 μg/kg。在恢复阶段，依托尼嗪的释放量减少至 2.4 ± 1 或 3.6 ± 1.5 μg/kg。

结论

乙醇自我给药观察到的刺激控制的减少似乎普遍适用于阿片类药物自我给药，表明刺激控制的这种变化可能在恢复中发挥普遍作用。