Oliva Idaira, Wanat Matthew J
Department of Biology, Neurosciences Institute, University of Texas at San Antonio , San Antonio, TX , USA.
Front Psychiatry. 2016 Mar 7;7:30. doi: 10.3389/fpsyt.2016.00030. eCollection 2016.
Drug-related behaviors in both humans and rodents are commonly thought to arise from aberrant learning processes. Preclinical studies demonstrate that the acquisition and expression of many drug-dependent behaviors involves the ventral tegmental area (VTA), a midbrain structure comprised of dopamine, GABA, and glutamate neurons. Drug experience alters the excitatory and inhibitory synaptic input onto VTA dopamine neurons, suggesting a critical role for VTA afferents in mediating the effects of drugs. In this review, we present evidence implicating the VTA in drug-related behaviors, highlight the diversity of neuronal populations in the VTA, and discuss the behavioral effects of selectively manipulating VTA afferents. Future experiments are needed to determine which VTA afferents and what neuronal populations in the VTA mediate specific drug-dependent behaviors. Further studies are also necessary for identifying the afferent-specific synaptic alterations onto dopamine and non-dopamine neurons in the VTA following drug administration. The identification of neural circuits and adaptations involved with drug-dependent behaviors can highlight potential neural targets for pharmacological and deep brain stimulation interventions to treat substance abuse disorders.
人类和啮齿动物中与药物相关的行为通常被认为源于异常的学习过程。临床前研究表明,许多药物依赖行为的习得和表现涉及腹侧被盖区(VTA),这是一个由多巴胺能、GABA能和谷氨酸能神经元组成的中脑结构。药物体验会改变作用于VTA多巴胺能神经元的兴奋性和抑制性突触输入,表明VTA传入神经在介导药物作用方面起着关键作用。在这篇综述中,我们展示了表明VTA参与药物相关行为的证据,强调了VTA中神经元群体的多样性,并讨论了选择性操纵VTA传入神经的行为效应。未来需要进行实验来确定哪些VTA传入神经以及VTA中的哪些神经元群体介导特定的药物依赖行为。对于确定药物给药后VTA中多巴胺能和非多巴胺能神经元上传入神经特异性的突触改变,进一步的研究也是必要的。识别与药物依赖行为相关的神经回路和适应性变化可以突出药理学和深部脑刺激干预治疗药物滥用障碍的潜在神经靶点。