Takahashi Taiki
Department of Cognitive and Behavioral Science, The University of Tokyo, Graduate School of Arts and Sciences, 3-8-1 Komaba, Meguro, Tokyo 153-8902, Japan.
Med Hypotheses. 2007;69(1):195-8. doi: 10.1016/j.mehy.2006.10.049. Epub 2006 Dec 29.
Loss of self-control in drug addicts (e.g. cocaine and amphetamine dependent patients) has been associated with hyperbolic discounting of delayed rewards (i.e., inconsistency in intertemporal choice). Neurobiophysical mechanisms underlying hyperbolic discounting are still unknown in spite of recent extensive work in neuroeconomics. Understanding of neuronal mechanisms of hyperbolic discounting is important for establishing neuropharmacological treatment of addiction. At the cognitive level, previous studies have indicated that psychophysics of time-estimation (i.e., Weber-Fechner law and Steven's power law of time-perception) may explain inconsistency in intertemporal choice. Regarding neuronal substrates of time-estimation, drugs of abuse dramatically change time-estimation, indicating that dopaminergic activities may mediate time-estimation. With respect to neuronal changes induced by drugs of abuse, recent studies have revealed that gap junction proteins (e.g., connexin 36) in dopamine neurons are increased by an self-administration of dopaminergic drugs such as cocaine and amphetamine. However, it has been yet to be examined how the enhanced electrical coupling due to substance administration induces addiction. Furthermore, a recent biophysical modelling study has demonstrated that the effect of the psychophysical laws are potentiated by non-synaptic electrical coupling between neurons via gap junctions. Based on these current findings, we hypothesized that hyperbolic discounting may be reduced to biophysical characteristics of dopamine neural circuits, that is, electrical coupling between time-encoding dopaminergic neurons via gap junctions. The present hypothesis states that drugs of abuse may induce addiction by exacerbating subject's impulsivity (a discount rate) and inconsistency (hyperbolicity) in intertemporal choice partly due to enhanced expression of gap junction proteins in dopaminergic neurons. Possible psychopharmacological treatments of impulsivity in drug addicts implied by our present hypothesis, e.g., administration of a gap junction blocker, are discussed.
吸毒者（如可卡因和苯丙胺依赖患者）的自我控制丧失与延迟奖励的双曲线贴现（即跨期选择的不一致性）有关。尽管最近神经经济学领域有大量研究，但双曲线贴现背后的神经生物物理机制仍然未知。理解双曲线贴现的神经元机制对于建立成瘾的神经药理学治疗方法很重要。在认知层面，先前的研究表明时间估计的心理物理学（即时间感知的韦伯 - 费希纳定律和史蒂文斯幂定律）可能解释跨期选择的不一致性。关于时间估计的神经元底物，滥用药物会显著改变时间估计，表明多巴胺能活动可能介导时间估计。关于滥用药物引起的神经元变化，最近的研究表明，多巴胺神经元中的缝隙连接蛋白（如连接蛋白36）会因可卡因和苯丙胺等多巴胺能药物的自我给药而增加。然而，药物给药导致的增强电耦合如何诱发成瘾尚未得到研究。此外，最近的一项生物物理建模研究表明，心理物理学定律的作用通过神经元间经由缝隙连接的非突触电耦合得到增强。基于这些当前发现，我们假设双曲线贴现可能归因于多巴胺神经回路的生物物理特性，即通过缝隙连接在时间编码多巴胺能神经元之间的电耦合。本假设指出，滥用药物可能通过加剧受试者在跨期选择中的冲动性（贴现率）和不一致性（双曲线性）来诱发成瘾，部分原因是多巴胺能神经元中缝隙连接蛋白的表达增强。我们讨论了本假设所暗示的对吸毒者冲动性可能的心理药理学治疗方法，例如给予缝隙连接阻滞剂。
