Department of Neurobiology, Duke University Medical Center, Durham, NC, USA.
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA.
Neuropsychopharmacology. 2018 Apr;43(5):953-963. doi: 10.1038/npp.2017.178. Epub 2017 Aug 25.
To determine the requirement for parvalbumin (PV) expressing GABAergic interneurons of the nucleus accumbens (NAc) in the behavioral adaptations induced by amphetamine (AMPH), we blocked synaptic vesicle release from these neurons using Cre-inducible viral expression of the tetanus toxin light chain in male and female PV-Cre mice. Silencing PV+ interneurons of the NAc selectively inhibited the expression of locomotor sensitization following repeated injections of AMPH and blocked AMPH-induced conditioned place preference (CPP). AMPH induced significantly more expression of the activity-dependent gene Fos in both D1 and D2 dopamine receptor-expressing medium spiny neurons (MSNs) of the NAc of PV+ interneuron silenced mice, suggesting a function for PV+ interneuron-mediated MSN inhibition in the expression of AMPH-induced locomotor sensitization and CPP. These data show a requirement for PV+ interneurons of the NAc in behavioral responses to AMPH, and they raise the possibility that modulation of PV+ interneuron function may alter the development or expression of psychostimulant-induced behavioral adaptations.
为了确定在安非他命（AMPH）诱导的行为适应中，伏隔核（NAc）中表达囊泡相关蛋白（PV）的 GABA 能中间神经元的需求，我们使用 Cre 诱导的破伤风毒素轻链病毒表达，在雄性和雌性 PV-Cre 小鼠中阻断这些神经元的突触囊泡释放。沉默 NAc 中的 PV+中间神经元选择性地抑制了重复注射 AMPH 后运动敏化的表达，并阻断了 AMPH 诱导的条件位置偏爱（CPP）。AMPH 在沉默 PV+中间神经元的小鼠的 NAc 中 D1 和 D2 多巴胺受体表达的中间神经元（MSNs）中诱导了显著更多的活性依赖性基因 Fos 的表达，这表明 PV+中间神经元介导的 MSN 抑制在 AMPH 诱导的运动敏化和 CPP 的表达中具有功能。这些数据表明 NAc 中的 PV+中间神经元在对 AMPH 的行为反应中具有必要性，并且它们提出了调节 PV+中间神经元功能可能改变精神兴奋剂诱导的行为适应的发展或表达的可能性。
