尼古丁中和大麻素多巴胺神经元突触可塑性作用

Neutralization of Synaptic Plasticity After Co-administration of HU210 and Nicotine in VTA Dopamine Neuron

目的观察尼古丁和大麻素(HU210)对腹侧被盖区(VTA)多巴胺(DA)神经元突触可塑性的影响,明确药物成瘾的神经机制和干预途径。方法将2个月龄SD大鼠分为对照组、HU210组、尼古丁组和HU210+尼古丁组。HU210组腹腔注射HU210,100μg·kg-1;尼古丁组皮下注射尼古丁0.5 mg·kg-1;HU210+尼古丁组腹腔注射HU210,剂量100μg·kg-1,并皮下注射尼古丁0.5 mg·kg-1;对照组腹腔及皮下注射Vehicle。均每日一次,连续5 d。最后一次注射后24 h对各组大鼠脑切片的VTA区进行高频电刺激(HFS)和低频电刺激(LFS),诱导长时程增强(LTP)和长时程抑制(LTD),观察场兴奋性突触后电位(f EPSP)幅度变化。结果与对照组比较,HU210组脑片可见LFS诱导出明显LTD,而HFS不能诱导LTP效应;尼古丁组HFS可诱导出LTP,LFS不能诱导出LTD;HU210+尼古丁组HFS不能诱导LTP效应,LFS不能诱导出LTD。结论慢性注射HU210易化了LFS对LTD的诱导,尼古丁可诱导LTP的产生,而大麻素诱导的LTD和尼古丁诱导的LTP具有中和效应。

Objective To investigate the effect of nicotine and cannabinoids on synaptic plasticity in the VTA dopamine neuron,and to explore the neuromechanism of drug addiction and to provide candidate therapeutic strategy for treating drug addiction. Methods Two-month old SD rats were randomly and equally divided into 4 groups： control group,HU210 group,nicotine group,and nicotine＋HU210 group.The HU210 group received HU210（ 100 μg·kg-1,intraperitoneal injection）once a day for 5 days. The nicotine group received nicotine（ 0. 5 mg·kg^-1,hypodermic injection） once a day for 5 days.The HU210＋ nicotine group received HU210（ 100 μg · kg-1,intraperitoneal injection） and nicotine（ 0.5 mg·kg-1,hypodermic injection） once a day for 5 days.Control group received vehicle intraperitoneal injection and hypodermic injection once a day for 5 days.High-frequency stimulation（ HFS） or low-frequency stimulation（ LFS） was given to induce long-term potentiation（ LTP） or long-term depression（ LTD） in VTA of each group 24 h after last injection,then field EPSPs（ f EPSPs） was recorded. Results It has been shown that LFS of VTA local excitatory afferents induced LTD after chronic injection（ once daily injections for 5 days） of HU210,while HFS could not induce LTP. HFS of VTA local excitatory afferents induced LTP after chronic injection（ once daily injections for 5 days） of nicotine,while LFS could not induce LTD.Daily chronic injection of nicotine and HU210 together prevented HFS-induced VTA LTP and LFS-induced VTA LTD. Conclusion Chronic injection of HU210 induces LTD and chronic injection of nicotine induces LTP.LTD and LTP can be neutralized after co-administration of HU210 and nicotine in VTA.