Department of Psychiatry and Behavioral Neuroscience, University of Chicago, 5841 S Maryland Ave, MC3077, Chicago, IL 60637, United States.
Neurosci Biobehav Rev. 2012 Jul;36(6):1565-76. doi: 10.1016/j.neubiorev.2012.04.005. Epub 2012 Apr 21.
Individuals vary in their initial reactions to drugs of abuse in ways that may contribute to the likelihood of subsequent drug use. In humans, most drugs of abuse produce positive subjective states such as euphoria and feelings of well-being, which may facilitate repeated use. In nonhumans, many drugs initially increase locomotor activity and produce discriminative stimulus effects, both of which have been considered to be models of human stimulant and subjective states. Both humans and nonhumans vary in their sensitivity to early acute drug effects in ways that may predict future use or self-administration, and some of these variations appear to be genetic in origin. However, it is not known exactly how the initial responses to drugs in either humans or nonhumans relate to subsequent use or abuse. In humans, positive effects of drugs facilitate continued use of a drug while negative effects discourage use, and in nonhumans, greater genetic risk for drug intake is predicted by reduced sensitivity to drug aversive effects; but whether these initial responses affect escalation of drug use, and the development of dependence is currently unknown. Although early use of a drug is a necessary step in the progression to abuse and dependence, other variables may be of greater importance in the transition from use to abuse. Alternatively, the same variables that predict initial acute drug effects and early use may significantly contribute to continued use, escalation and dependence. Here we review the existing evidence for relations between initial direct drug effects, early use, and continued use. Ultimately, these relations can only be determined from systematic longitudinal studies with comprehensive assessments from early drug responses to progression of problem drug use. In parallel, additional investigation of initial responses in animal models as predictors of drug use will shed light on the underlying mechanisms.
个体对滥用药物的初始反应存在差异，这些差异可能会影响他们后续使用药物的可能性。在人类中，大多数滥用药物会产生积极的主观状态，如欣快和幸福感，这可能会促使他们重复使用。在非人类动物中，许多药物最初会增加运动活动并产生辨别性刺激效应，这两者都被认为是人类兴奋剂和主观状态的模型。人类和非人类对早期急性药物效应的敏感性存在差异，这些差异可能预测他们未来的使用或自我给药情况，其中一些差异似乎具有遗传起源。然而，目前尚不清楚人类或非人类对药物的初始反应与随后的使用或滥用之间的关系。在人类中，药物的积极效应促使人们继续使用药物，而消极效应则阻止人们使用药物；在非人类动物中，对药物厌恶效应的敏感性降低预示着更大的药物摄入遗传风险；但这些初始反应是否会影响药物使用的升级以及依赖的发展目前尚不清楚。尽管早期使用药物是向滥用和依赖发展的必要步骤，但其他变量在从使用到滥用的转变中可能更为重要。或者，预测初始急性药物效应和早期使用的相同变量可能会显著影响持续使用、升级和依赖。在这里，我们回顾了初始直接药物效应、早期使用和持续使用之间关系的现有证据。最终，只有通过对早期药物反应到问题药物使用进展进行全面评估的系统纵向研究，才能确定这些关系。与此同时，对动物模型中初始反应作为药物使用预测指标的进一步研究将有助于阐明潜在的机制。
