Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
Pharmacol Biochem Behav. 2022 Oct;220:173462. doi: 10.1016/j.pbb.2022.173462. Epub 2022 Sep 7.
Cocaine use disorder occurs in an environment where cocaine and other nondrug commodities are concurrently available. Preclinical drug-vs-nondrug choice procedures are one simplified method of modeling this complex clinical environment. The present study established a discrete-trial cocaine-vs-social interaction choice procedure in male and female rats and determined sensitivity of choice behavior to manipulations of reinforcer magnitude and non-contingent "sample" reinforcer presentation. Rats could make up to nine discrete choices between an intravenous cocaine infusion (0.1-1.0 mg/kg/inf) and social interaction with a same-sex social "Partner" rat. Cocaine infusions were available under a progressive-ratio (PR) schedule of reinforcement, and social interaction was available under a fixed-ratio (FR) 3 schedule. Social interaction was chosen over no or small cocaine doses (saline, 0.01 mg/kg/inf) and behavior was reallocated away from social and towards cocaine at larger cocaine doses (1.0 mg/kg/inf). Manipulating social interaction time as one method to alter social reinforcer magnitude did not significantly alter cocaine-vs-social choice. Removing the non-contingent reinforcer presentations before the discrete choice trials also failed to affect cocaine-vs-social choice, suggesting the time interval was sufficient to minimize any potential influence of the non-contingent cocaine infusions on subsequent choice behavior. Overall, the present results were consistent with previous drug-vs-social choice studies and extend our knowledge of environmental factors impacting drug-vs-social choice. Future studies determining the pharmacological sensitivity of cocaine-vs-social choice will be important in expanding the preclinical utility of these procedures for candidate medication drug development.
可卡因使用障碍发生在同时存在可卡因和其他非药物商品的环境中。临床前药物与非药物选择程序是模拟这种复杂临床环境的一种简化方法。本研究在雄性和雌性大鼠中建立了离散试验可卡因与社交互动的选择程序，并确定了选择行为对强化物大小和非偶然“样本”强化物呈现的操纵的敏感性。大鼠可以在静脉内可卡因输注（0.1-1.0mg/kg/inf）和与同性别社交“伙伴”大鼠的社交互动之间进行多达九次离散选择。可卡因输注可根据递增比率（PR）强化计划获得，社交互动可根据固定比率（FR）3 计划获得。大鼠选择社交互动而不是没有或小剂量的可卡因（生理盐水，0.01mg/kg/inf），并且在较大剂量的可卡因（1.0mg/kg/inf）下，行为从社交重新分配到可卡因。操纵社交互动时间作为改变社交强化物大小的一种方法并没有显著改变可卡因与社交的选择。在离散选择试验之前去除非偶然的强化物呈现也未能影响可卡因与社交的选择，这表明时间间隔足以最大限度地减少非偶然的可卡因输注对随后的选择行为的任何潜在影响。总体而言，目前的结果与之前的药物与社交选择研究一致，并扩展了我们对影响药物与社交选择的环境因素的了解。未来确定可卡因与社交选择的药理学敏感性的研究对于扩大这些程序在候选药物药物开发中的临床前效用将非常重要。
