Yuen Jason, Goyal Abhinav, Rusheen Aaron E, Kouzani Abbas Z, Berk Michael, Kim Jee Hyun, Tye Susannah J, Blaha Charles D, Bennet Kevin E, Lee Kendall H, Shin Hojin, Oh Yoonbae
Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, United States.
The Institute for Mental and Physical Health and Clinical Translation (IMPACT), Barwon Health, Deakin University, Geelong, VIC, Australia.
Front Neurosci. 2023 Jan 30;17:1061578. doi: 10.3389/fnins.2023.1061578. eCollection 2023.
Cocaine's addictive properties stem from its capacity to increase tonic extracellular dopamine levels in the nucleus accumbens (NAc). The ventral tegmental area (VTA) is a principal source of NAc dopamine. To investigate how high frequency stimulation (HFS) of the rodent VTA or nucleus accumbens core (NAcc) modulates the acute effects of cocaine administration on NAcc tonic dopamine levels multiple-cyclic square wave voltammetry (M-CSWV) was used. VTA HFS alone decreased NAcc tonic dopamine levels by 42%. NAcc HFS alone resulted in an initial decrease in tonic dopamine levels followed by a return to baseline. VTA or NAcc HFS following cocaine administration prevented the cocaine-induced increase in NAcc tonic dopamine. The present results suggest a possible underlying mechanism of NAc deep brain stimulation (DBS) in the treatment of substance use disorders (SUDs) and the possibility of treating SUD by abolishing dopamine release elicited by cocaine and other drugs of abuse by DBS in VTA, although further studies with chronic addiction models are required to confirm that. Furthermore, we demonstrated the use of M-CSWV can reliably measure tonic dopamine levels with both drug administration and DBS with minimal artifacts.
可卡因的成瘾特性源于其增加伏隔核(NAc)中细胞外多巴胺基础水平的能力。腹侧被盖区(VTA)是NAc多巴胺的主要来源。为了研究对啮齿动物VTA或伏隔核核心(NAcc)进行高频刺激(HFS)如何调节可卡因给药对NAc多巴胺基础水平的急性影响,采用了多循环方波伏安法(M-CSWV)。单独进行VTA HFS可使NAc多巴胺基础水平降低42%。单独进行NAcc HFS会导致多巴胺基础水平最初下降,随后恢复到基线。在可卡因给药后进行VTA或NAcc HFS可阻止可卡因引起的NAc多巴胺基础水平升高。目前的结果表明,在治疗物质使用障碍(SUDs)时,NAc深部脑刺激(DBS)可能存在潜在机制,并且有可能通过VTA中的DBS消除可卡因和其他滥用药物引起的多巴胺释放来治疗SUD,不过需要使用慢性成瘾模型进行进一步研究来证实这一点。此外,我们证明了使用M-CSWV能够在药物给药和DBS过程中可靠地测量多巴胺基础水平,且伪迹最少。