Transition to drug addiction: a negative reinforcement model based on an allostatic decrease in reward function
Transition to drug addiction: a negative reinforcement model based on an allostatic decrease in reward function
复制标题
DOI：
10.1007/s00213-005-2180-z
复制
发表时间：
2005-07-01
影响因子：
3.4
通讯作者：
Koob, GF
中科院分区：
文献类型：
--
作者：
Ahmed, SH;Koob, GF
基本原理：从最初的药物使用到药物成瘾的转变被认为是由大脑反奖赏过程的过度激活驱动的奖赏功能的非稳态下降引起的。目的：奖赏功能的下降如何解释强迫性药物使用目前还不完全清楚，仍然是一个争论的主题。我们提出了一个定量模型可卡因自我管理，整合药代动力学，药效学和动机因素来解决这个问题。该模型假设，奖励系统的响应是一个稳态调节的过程，其中所需的响应水平（称为奖励设定点）最初不同于基线水平。结果：通过计算机模拟获得的理论数据与在动物自我施用可卡因中获得的实验数据相拟合（即，自我注射的疗程内模式、剂量-注射函数的形状和曲率、药物摄入和调节药物效果之间的非线性关系）。重要的是，奖励系统反应性的变稳态降低的模拟加剧了驱动自我给药的初始错误，从而增加了药物的摄入量和动力。这种变应性的变化表现为一个垂直转移的剂量注射功能中看到的动物与不断升级的可卡因自我administration.Conclusions：本模型提供了一个令人满意的解释升级的药物摄入量，并提出了一种新的负强化成瘾的基础上变应性减少奖励功能。
Rationale: The transition from initial drug use to drug addiction has been proposed to result from an allostatic decrease in reward function driven by an over-activation of brain antireward processes.Objectives: How decreased reward function explains compulsive drug use is not entirely clear at present, and is still a subject for debate.Methods: We present a quantitative model of cocaine self-administration that integrates pharmacokinetic, pharmacodynamic, and motivational factors to address this question. The model assumes that reward system responsivity is a homeostatically regulated process where the desired level of responsivity ( called the reward set point) is initially different from the baseline level. The reduction or correction of this difference or error in reward function would drive cocaine self-administration.Results: Theoretical data obtained by computer simulation fit the experimental data obtained in animals self-administering cocaine (i.e.,the within-session pattern of self-injections, the shape and curvature of the dose-injection function, the nonlinear relationship between drug intake and regulated drug effects). Importantly, simulation of an allostatic decrease in reward system responsivity exacerbates the initial error that drives self-administration, thereby increasing both the intake of, and the motivation for, the drug. This allostatic change manifests as a vertical shift in the dose-injection function similar to that seen in animals with escalating cocaine self-administration.Conclusions: The present model provides a satisfactory explanation of escalated drug intake and suggests a novel negative reinforcement view of addiction based on an allostatic decrease in reward function.