Interactive influences of catecholamines and corticotropin-releasing factor in anxiety responses and the reinstatement of cocaine seeking in rats: role of withdrawal duration

已经取得了显着的进展，对表征基本的神经生物学基板的基础上重新药物寻求大鼠。 这项工作的核心是基于复发动物模型的研究，称为恢复程序。 在该程序中，训练动物对药物输注进行行为反应。 随后，通过拒绝药物消除该行为，此时通过暴露于事件（例如药物的启动注射、暴露于药物相关线索或暴露于压力源）触发药物寻求的恢复。 复吸研究中需要考虑的一个重要因素是停药持续时间。事实上，动机和相应的神经生物学因素影响恢复的倾向，在一个时间后终止服用药物可能是非常不同的，在另一个时间。 拟议的实验的目的是提供一个系统的调查之间的关系，焦虑反应和恢复可卡因寻求作为一个功能的戒断时间，和相应的神经过程。 该提案的一般假设是，特定的应激反应脑回路（包括含有神经化学物质促肾上腺皮质激素释放因子、去甲肾上腺素和多巴胺的脑回路）内的活动平衡随着可卡因自我给药终止后的时间推移而变化，这些变化反映在行为中，包括焦虑样行为的表达和应激诱导的可卡因寻求恢复。此外，据推测，引起焦虑样反应的条件和可卡因寻求的压力诱导的恢复之间缺乏对应关系。 这项工作是很重要的了解动机因素，影响恢复响应在不同的时间后终止药物自我管理，更普遍的是，对澄清介导成瘾，恢复，和药物寻求的机制。

Significant advances have been made toward characterizing the basic neurobiological substrates underlying renewed drug seeking in rats. Central to this effort are studies based on an animal model of relapse, known as the reinstatement procedure. In this procedure, an animal is trained to perform a behavioural response for drug infusions. Subsequently, the behaviour is extinguished by withholding drug, at which time the reinstatement of drug seeking is triggered by exposure to an event, such as a priming injection of drug, exposure to drug-associated cues, or exposure to a stressor. An important factor to consider in the study of reinstatement is withdrawal duration. Indeed, the motivational and corresponding neurobiological factors affecting the propensity for reinstatement at one time following termination of drug taking may be very different than at another time. The proposed experiments are designed to provide a systematic investigation of the relationship between anxiety responses and reinstatement of cocaine seeking as a function of withdrawal duration, and the corresponding neuronal processes. The general hypothesis of the proposal is that the balance of activity within specific stress-responsive brain circuits, including those containing the neurochemicals corticotropin-releasing factor, noradrenaline, and dopamine, changes depending on time lapsed since the termination of cocaine self-administration, and these changes are reflected in behaviour, including the expression of anxiety-like behaviour and stress-induced reinstatement of cocaine seeking. Furthermore, it is hypothesized that there is a lack of correspondence between conditions that elicit anxiety-like responses and the stress-induced reinstatement of cocaine seeking. This work is important toward understanding the motivational factors that influence reinstatement responding at different times following the termination of drug self-administration and, more generally, toward clarifying the mechanisms mediating addiction, reinstatement, and drug seeking.