Davidson C, Ellinwood E H, Lee T H
Department of Psychiatry, Duke University Medical Center, Durham, NC 27710, USA.
Brain Res Bull. 2000 Jan 1;51(1):89-93. doi: 10.1016/s0361-9230(99)00213-0.
Using slice preparations, we investigated the effects of chronic cocaine treatment on dopamine autoreceptor sensitivity in the nucleus accumbens core. Cocaine (40 mg/kg/day) was given for 14 days, either by continuous subcutaneous infusion (osmotic minipumps) or single daily injections. One or 7 days after cocaine withdrawal, we used fast scan cyclic voltammetry (10 Hz sampling rate) to measure inhibition of electrically evoked dopamine release by quinpirole (3-300 nM). Continuous cocaine infusion increased quinpirole sensitivity on day 1 of withdrawal, particularly at low concentrations of quinpirole, but this effect was no longer evident by day 7. Intermittent cocaine injections had no effect on day 1 of withdrawal but by day 7 there was a quinpirole subsensitivity. On either withdrawal day, the baseline peak dopamine release or uptake half-life exhibited no treatment group differences. It is suggested that these cocaine dosing regimes cause differential and dynamic changes in dopamine autoreceptor sensitivity during the early withdrawal phase.
我们使用脑片制备技术，研究了长期给予可卡因对伏隔核核心区多巴胺自身受体敏感性的影响。通过持续皮下输注（渗透微型泵）或每日单次注射给予可卡因（40毫克/千克/天），持续14天。在可卡因戒断1天或7天后，我们使用快速扫描循环伏安法（采样率10赫兹）来测量喹吡罗（3 - 300纳摩尔）对电诱发多巴胺释放的抑制作用。持续输注可卡因在戒断第1天增加了喹吡罗敏感性，尤其是在低浓度喹吡罗时，但到第7天这种效应不再明显。间歇性注射可卡因在戒断第1天没有影响，但到第7天出现了喹吡罗敏感性降低。在任何一个戒断日，多巴胺释放基线峰值或摄取半衰期在各治疗组之间均无差异。提示这些可卡因给药方案在早期戒断阶段会导致多巴胺自身受体敏感性出现不同的动态变化。
