Aarde S M, Huang P K, Dickerson T J, Taffe M A
Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, SP30-2400, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
Psychopharmacology (Berl). 2015 Jun;232(11):1867-77. doi: 10.1007/s00213-014-3819-4. Epub 2014 Nov 26.
Lack of access to conventional sources of reinforcement has been proposed as a risk factor for substance abuse in lower socioeconomic populations. There is laboratory evidence that behavioral alternatives (enrichment or exercise) and alternative reinforcers (e.g., sweetened solutions) can reduce self-administration of a variety of drugs.
The objective of this study is to determine if drug self-administration could devalue wheel activity in an animal model.
Male Wistar rats were trained to self-administer 3,4-methylenedioxypyrovalerone (MDPV; "bath salts"), 0.05 mg/kg/infusion, i.v., with concurrent access to a running wheel that was either locked (LW) or unlocked (UW).
MDPV intake steadily increased across the 20-session acquisition interval but did not differ significantly between UW and LW groups. Mean wheel rotations declined significantly across the acquisition interval in the UW group. Of the rats that acquired self-administration, 60 % engaged in a binge-like behavior at the initiation of acquisition; intake was limited only by post-reinforcement time-out. The binge rats had higher post-acquisition levels of drug intake (even after excluding the binge session), and the UW binge rats showed a precipitous post-acquisition drop in wheel activity that was not observed in the UW no-binge rats.
These data confirm that MDPV is a powerful reward/reinforcer and show that a relatively high rate of intake at the onset of drug taking can devalue natural rewards (wheel activity) and can predict higher subsequent drug intake levels. Thus, limiting the intensity of initial drug exposure may attenuate subsequent drug abuse/addiction by preventing the devaluation of natural alternative rewards/reinforcers.
获得常规强化源的机会不足被认为是社会经济地位较低人群药物滥用的一个风险因素。有实验室证据表明,行为替代方式(丰富环境或运动)和替代强化物(如甜味溶液)可以减少多种药物的自我给药。
本研究的目的是确定在动物模型中药物自我给药是否会降低转轮活动的价值。
雄性Wistar大鼠经训练以静脉注射方式自我给药3,4-亚甲基二氧吡咯戊酮(MDPV;“浴盐”),剂量为0.05mg/kg/次,同时可使用一个锁定(LW)或未锁定(UW)的转轮。
在20次获取实验期间,MDPV的摄入量稳步增加,但UW组和LW组之间无显著差异。UW组的平均转轮转动次数在获取实验期间显著下降。在学会自我给药的大鼠中,60%在获取实验开始时出现类似暴饮暴食的行为;摄入量仅受强化后超时的限制。暴饮暴食的大鼠在获取实验后的药物摄入量较高(即使排除暴饮暴食的实验期),UW组暴饮暴食的大鼠在获取实验后转轮活动急剧下降,而UW组未暴饮暴食的大鼠未出现这种情况。
这些数据证实MDPV是一种强大的奖赏/强化物,并表明在开始用药时相对较高的摄入量会降低自然奖赏(转轮活动)的价值,并可预测随后更高的药物摄入量。因此,限制初始药物暴露的强度可能通过防止自然替代奖赏/强化物的贬值来减轻随后的药物滥用/成瘾。