Canales Juan J
Behavioural Neuroscience, Department of Psychology, The University of Canterbury, Private Bag 4800, 8140, Christchurch, New Zealand,
Curr Top Behav Neurosci. 2013;15:293-312. doi: 10.1007/7854_2012_230.
Addiction is a complex neuropsychiatric disorder which causes disruption at multiple levels, including cognitive, emotional, and behavioral domains. Traditional biological theories of addiction have focused on the mesolimbic dopamine pathway and the nucleus accumbens as anatomical substrates mediating addictive-like behaviors. More recently, we have begun to recognize the engagement and dynamic influence of a much broader circuitry which encompasses the frontal cortex, the amygdala, and the hippocampus. In particular, neurogenesis in the adult hippocampus has become a major focus of attention due to its ability to influence memory, motivation, and affect, all of which are disrupted in addiction. First, I summarize toxicological data that reveal strongly suppressive effects of drug exposure on adult hippocampal neurogenesis. Then, I discuss the impact of deficient neurogenesis on learning and memory function, stress responsiveness and affective behavior, as they relate to addiction. Finally, I examine recent behavioral observations that implicate neurogenesis in the adult hippocampus in the emergence and maintenance of addictive behavior. The evidence reviewed here suggests that deficient neurogenesis is associated with several components of the downward spiraling loop that characterizes addiction, including elevated sensitivity to drug-induced reward and reinforcement, enhanced neurohormonal responsiveness, emergence of a negative affective state, memory impairment, and inflexible behavior.
成瘾是一种复杂的神经精神障碍，它会在多个层面造成破坏，包括认知、情感和行为领域。传统的成瘾生物学理论主要关注中脑边缘多巴胺通路和伏隔核，将其视为介导成瘾样行为的解剖学基础。最近，我们开始认识到一个更广泛的神经回路的参与及其动态影响，这个回路包括额叶皮质、杏仁核和海马体。特别是，成年海马体中的神经发生因其能够影响记忆、动机和情感而成为主要关注焦点，而这些在成瘾过程中都会受到干扰。首先，我总结了毒理学数据，这些数据揭示了药物暴露对成年海马体神经发生具有强烈的抑制作用。然后，我讨论了神经发生不足对学习和记忆功能、应激反应性及情感行为的影响，因为它们与成瘾有关。最后，我研究了最近的行为观察结果，这些结果表明成年海马体中的神经发生与成瘾行为的出现和维持有关。这里所综述的证据表明，神经发生不足与成瘾所特有的恶性循环的几个组成部分有关，包括对药物诱导的奖赏和强化的敏感性增加、神经激素反应性增强、负面情感状态的出现、记忆障碍和行为僵化。
