Effects of intermittent and continuous cocaine administration on dopamine release and uptake regulation in the striatum: In vitro voltammetric assessment
Effects of intermittent and continuous cocaine administration on dopamine release and uptake regulation in the striatum: In vitro voltammetric assessment
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DOI：
10.1007/bf02247384
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发表时间：
1996-08-01
影响因子：
3.4
通讯作者：
Ellinwood, EH
中科院分区：
文献类型：
--
作者：
Jones, SR;Lee, TH;Ellinwood, EH
慢性每日注射可卡因诱导行为敏感随后的可卡因挑战，而连续输注诱导耐受。在7天的停药期后，我们检查了这两种给药方案对以下方面的影响：（1）单脉冲电刺激后的基线多巴胺外排和摄取，（2）可卡因对摄取的抑制，以及（3）自身受体激活对外排的抑制。大鼠连续14天通过渗透微泵或间歇性每日一次注射给予考地平（40 mg/kg/天）。对照组植入含生理盐水的微型泵。停药7天后，使用体外快速扫描循环伏安法检查尾状核中的多巴胺动力学。该技术提供了细胞外空间中多巴胺的非常快速的测量。因此，当结合单脉冲电刺激诱发的内源性多巴胺外排时，可以直接测量外排的释放和摄取成分。在没有药理学试剂的情况下，在基线多巴胺释放量或摄取动力学方面没有发现组间差异;浴用可卡因（0.03-60 μ M）抑制摄取的效力在任一组中也没有改变。相比之下，喹吡罗（一种自身受体激动剂，5-250 nM）的效力分别在可卡因注射组和泵组中显著降低和增加。因此，产生致敏作用的可卡因给药方案导致调节释放的自身受体的功能性亚敏感性，而产生耐受性的方案导致自身受体超敏感性。
Chronic daily injections of cocaine induce behavioral sensitization to subsequent cocaine challenge, while continuous infusion induces tolerance. Following a 7-day withdrawal period, we examined the effects of these two dosing regimens on: (1) baseline dopamine efflux and uptake following single-pulse electrical stimulation, (2) inhibition of uptake by cocaine; and (3) inhibition of efflux by autoreceptor activation. Cocaine (40 mg/kg per day) was administered to rats for 14 days either continuously by osmotic minipumps or intermittently by once-a-day injections. Minipumps containing saline were implanted in the control group. After 7 days of withdrawal, dopamine kinetics in the caudate was examined using in vitro fast-scan cyclic voltammetry. This technique provides very rapid measurements of dopamine in the extracellular space. Thus, when combined with endogenous dopamine efflux evoked by single-pulse, electrical stimulations, it was possible directly to measure the release and uptake components of the efflux. In the absence of pharmacological agents, no group differences were found in the amount of baseline dopamine released or in the uptake kinetics; the potency of bath-applied cocaine (0.03-60 mu M) in inhibiting the uptake was also unaltered in either group. In contrast, the potency of quinpirole (an autoreceptor agonist, 5-250 nM) was significantly decreased and increased in the cocaine injection and pump groups, respectively. Thus, the cocaine administration regimen which produces sensitization results in a functional subsensitivity of release-modulating autoreceptors, while the tolerance-producing regimen results in autoreceptor supersensitivity.