Yan Qing-Shan, Zheng Shi-Zhong, Feng Mei-Jiang, Yan Shu-E
Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine, Peoria, IL 61656, USA.
Brain Res. 2005 Oct 26;1060(1-2):126-37. doi: 10.1016/j.brainres.2005.08.051. Epub 2005 Oct 5.
Evidence suggests that 5-hydroxytriptamine-1B (5-HT1B) receptors play a role in modifying ethanol's reinforcing effects and voluntary intake, and that 5-HT1B receptors within the ventral tegmental area (VTA) are involved in regulation of mesolimbic dopaminergic neuronal activity. Since increased mesolimbic dopaminergic transmission has been implicated in ethanol's reinforcing properties, this study was designed to assess the involvement of VTA 5-HT1B receptors in mediating the stimulatory effects of ethanol on VTA dopaminergic neurons. Dual-probe microdialysis was performed in freely moving adult Sprague-Dawley rats with one probe within the VTA and the other within the ipsilateral nucleus accumbens (NACC). Dopamine (DA) levels in dialysates from both areas, as the index of the activity of mesolimbic DA neurons, were measured simultaneously. The results showed that intraperitoneal injection of ethanol at the doses of 1 and 2 g/kg increased extracellular DA concentrations in both the VTA and the NACC, suggesting increased DA neuronal activity. These ethanol-induced increases of the DA release in the VTA and the NACC were significantly attenuated by intra-tegmental infusion of SB 216641 (a 5-HT(1B) receptor antagonist), but not BRL 15572 (a 5-HT(1D/1A) receptor antagonist) or WAY 100635 (a 5-HT1A receptor antagonist). Administration of ethanol at the same doses did not significantly alter extracellular levels of GABA in the VTA. The results also showed that intra-tegmental infusion of CP 94253, a 5-HT1B receptor agonist, significantly prolonged the effects of ethanol on NACC DA. The results suggest that blockade and activation of VTA 5-HT1B receptors attenuates and potentiates the neurochemical effects of ethanol, respectively, and support the suggestion that VTA 5-HT(1B) receptors may be involved in part in mediating the activating effects of ethanol on mesolimbic DA neurons.
有证据表明，5-羟色胺-1B（5-HT1B）受体在改变乙醇的强化作用和自主摄入量方面发挥作用，并且腹侧被盖区（VTA）内的5-HT1B受体参与中脑边缘多巴胺能神经元活动的调节。由于中脑边缘多巴胺能传递增加与乙醇的强化特性有关，本研究旨在评估VTA 5-HT1B受体在介导乙醇对VTA多巴胺能神经元的刺激作用中的参与情况。在自由活动的成年Sprague-Dawley大鼠中进行双探针微透析，一个探针置于VTA内，另一个置于同侧伏隔核（NACC）内。同时测量来自这两个区域的透析液中的多巴胺（DA）水平，作为中脑边缘DA神经元活动的指标。结果表明，腹腔注射1和2 g/kg剂量的乙醇可增加VTA和NACC中的细胞外DA浓度，表明DA神经元活动增强。VTA内注射SB 216641（一种5-HT(1B)受体拮抗剂）可显著减弱乙醇诱导的VTA和NACC中DA释放的增加，但BRL 15572（一种5-HT(1D/1A)受体拮抗剂）或WAY 100635（一种5-HT1A受体拮抗剂）则无此作用。相同剂量的乙醇给药并未显著改变VTA中GABA的细胞外水平。结果还表明，VTA内注射5-HT1B受体激动剂CP 94253可显著延长乙醇对NACC DA的作用。结果表明，阻断和激活VTA 5-HT1B受体分别减弱和增强了乙醇的神经化学作用，并支持VTA 5-HT(1B)受体可能部分参与介导乙醇对中脑边缘DA神经元的激活作用这一观点。
