Cocaine, amphetamine, and methamphetamine abuse disorders are serious worldwide health problems. To date, there are no FDA-approved medications for the treatment of these disorders. Elucidation of the biochemical underpinnings contributing to psychostimulant addiction is critical for the development of effective therapies. Excitatory signaling and glutamate homeostasis are well known pathophysiological substrates underlying addiction-related behaviors spanning multiple types of psychostimulants. To alleviate relapse behavior to psychostimulants, considerable interest has focused on GLT-1, the major glutamate transporter in the brain. While many brain regions are implicated in addiction behavior, this review focuses on two regions well known for their role in mediating the effects of cocaine and amphetamines, namely the nucleus accumbens (NAc) and the ventral tegmental area (VTA). In addition, because many investigators have utilized Cre-driver lines to selectively control gene expression in defined cell populations relevant for psychostimulant addiction, we discuss potential off-target effects of Cre-recombinase that should be considered in the design and interpretation of such experiments.

可卡因、苯丙胺和甲基苯丙胺滥用障碍是严重的全球健康问题。迄今为止，还没有 FDA 批准的用于治疗这些疾病的药物。阐明导致精神兴奋剂成瘾的生化基础对于开发有效疗法至关重要。兴奋性信号传导和谷氨酸稳态是众所周知的跨越多种精神兴奋剂的成瘾相关行为的病理生理学底物。为了减轻对精神兴奋剂的复发行为，人们对大脑中主要的谷氨酸转运蛋白 GLT-1 产生了相当大的兴趣。虽然许多大脑区域与成瘾行为有关，但本综述侧重于两个区域，这些区域以其在调节可卡因和安非他明的影响方面的作用而闻名，即伏隔核（NAc）和腹侧被盖区（VTA）。此外，由于许多研究人员已经利用 Cre 驱动系来选择性地控制与精神兴奋剂成瘾相关的特定细胞群中的基因表达，我们讨论了在设计和解释此类实验时应考虑的 Cre 重组酶的潜在脱靶效应。