Zhao Ning, Wang Hoau-Yan, Dow-Edwards Diana
Department of Physiology and Pharmacology, SUNY Downstate Medical Center, Brooklyn, NY, United States.
Neurosci Lett. 2008 Jun 20;438(2):159-62. doi: 10.1016/j.neulet.2008.04.014. Epub 2008 Apr 10.
The effect of cocaine exposure during early postnatal ages on coupling of dopamine (DA) D(1)- and D(2)-like receptors to their respective Gs/olf and Gi was examined in striatum and medial frontal cortex (MFC). Sprague-Dawley rats were subcutaneously injected with either 50 mg/kg cocaine or vehicle during postnatal day (PnD) 11-20 and dopaminergic D(1)- and D(2)-like receptor signaling was evaluated at PnD 60. Results showed that cocaine exposure did not affect the magnitude of both DA D(1)- and D(2)-like receptor coupling to their respective Gs/olf and Gi in striatum. However, in the medial frontal cortex, the basal and the DA D(1)-like receptor and Gs association were reduced in cocaine-exposed brains. However, there was no change in basal or DA D(2)-like receptor-Gi linkage in medial frontal cortex. Since frontal cortex plays a critical role in regulating cognition and working memory, disruption of DA-modulated circuits or alteration of dopaminergic activity resulting from postnatal cocaine exposure may result in abnormal responses to environmental challenges leading to long-term behavioral changes.
研究了出生后早期接触可卡因对纹状体和内侧前额叶皮质（MFC）中多巴胺（DA）D1和D2样受体与其各自的Gs/olf和Gi偶联的影响。在出生后第11 - 20天，给Sprague-Dawley大鼠皮下注射50 mg/kg可卡因或赋形剂，并在出生后第60天评估多巴胺能D1和D2样受体信号传导。结果显示，接触可卡因并不影响纹状体中DA D1和D2样受体与其各自的Gs/olf和Gi偶联的程度。然而，在内侧前额叶皮质中，接触可卡因的大脑中基础状态以及DA D1样受体与Gs的关联减少。然而，内侧前额叶皮质中基础状态或DA D2样受体与Gi的联系没有变化。由于前额叶皮质在调节认知和工作记忆中起关键作用，出生后接触可卡因导致的DA调节回路破坏或多巴胺能活性改变可能导致对环境挑战的异常反应，从而导致长期行为变化。
