Self David W
Department of Psychiatry, The Seay Center for Basic and Applied Research in Psychiatric Illness, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9070, USA.
Neuropharmacology. 2004;47 Suppl 1:242-55. doi: 10.1016/j.neuropharm.2004.07.005.
Previous studies have identified several neuroadaptations to chronic drug use, but relatively few have been functionally linked to addiction-related changes in drug-taking and -seeking behaviors. This article summarizes our past and present studies on the contribution of drug-induced neuroadaptations in the mesolimbic dopamine system to addiction-related changes in drug self-administration and the propensity for relapse in drug withdrawal. Our studies suggest that drug-induced up-regulation in cyclic AMP (cAMP)-protein kinase A (PKA) signaling in the nucleus accumbens (NAc) contributes to escalating drug intake and a propensity for relapse by differentially altering the sensitivity of D1 and D2 dopamine receptors that regulate drug-taking and -seeking behaviors. In addition, our studies suggest that drug-induced neuroplasticity at excitatory synapses in both the ventral tegmental area (VTA) and the NAc also facilitates drug-seeking behavior and the propensity for relapse. Finally, the role of both transient and enduring neuroadaptations in regulating drug-seeking behavior is discussed in view of different learning- and memory-based interactions.
先前的研究已经确定了几种对慢性药物使用的神经适应性变化，但相对较少的研究在功能上与药物摄取和觅药行为中与成瘾相关的变化联系起来。本文总结了我们过去和现在关于中脑边缘多巴胺系统中药物诱导的神经适应性变化对药物自我给药中与成瘾相关的变化以及药物戒断后复发倾向的贡献的研究。我们的研究表明，伏隔核（NAc）中药物诱导的环磷酸腺苷（cAMP）-蛋白激酶A（PKA）信号上调，通过差异性改变调节药物摄取和觅药行为的D1和D2多巴胺受体的敏感性，导致药物摄入量增加和复发倾向。此外，我们的研究表明，腹侧被盖区（VTA）和NAc中兴奋性突触处药物诱导的神经可塑性也促进了觅药行为和复发倾向。最后，鉴于基于不同学习和记忆的相互作用，讨论了短暂和持久神经适应性变化在调节觅药行为中的作用。
