Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology Polish Academy of Sciences, Poland.
Addict Biol. 2013 Mar;18(2):307-24. doi: 10.1111/adb.12031. Epub 2013 Jan 14.
We investigated the changes in dopamine (DA), glutamate and γ-aminobutyric acid (GABA) during cocaine self-administration in rats implanted with guide cannulae into the nucleus accumbens and ventral pallidum. After stabilized cocaine self-administration, separate groups of rats underwent extinction (10 days) procedure in which cocaine infusion was replaced by saline injections. With using a 'yoked' procedure, the effects of cocaine or its withdrawal on the level of neurotransmitters were evaluated by dual-probe microdialysis. Repeated cocaine administration reduced basal glutamate levels in the nucleus accumbens and ventral pallidum, whereas it did not affect basal accumbal DA levels. Only rats that self-administered cocaine had increased basal GABA overflow in both examined brain structures. Active or passive cocaine administration elevated extracellular accumbal DA, however, the extent of cocaine-evoked DA level was significantly higher in rats that self-administered cocaine while both groups of animals showed also an attenuation of GABA level in the nucleus accumbens. On day 10 of extinction training, rats previously given cocaine revealed decreases in the basal accumbal concentration of glutamate while the basal GABA levels were significantly enhanced as compared with baseline of saline-yoked controls. Potassium depolarization delayed the reduction of the accumbal and pallidal extracellular glutamate levels in the active and passive cocaine groups. The present data indicate that changes in DA and GABA neurotransmission during maintenance phase mirror the motivational aspects of cocaine intake. Depending on acute (24 hours) or late (10 days) cocaine withdrawal, different neurotransmitter systems (i.e. glutamate or GABA) seem to be involved.
我们研究了在植入导水管到伏隔核和腹侧苍白球的大鼠中，可卡因自我给药期间多巴胺（DA）、谷氨酸和γ-氨基丁酸（GABA）的变化。在稳定的可卡因自我给药后，单独的大鼠组接受了消退（10 天）程序，其中可卡因输注被盐水注射取代。通过使用“对偶”程序，通过双探针微透析评估可卡因或其戒断对神经递质水平的影响。重复可卡因给药降低了伏隔核和腹侧苍白球中的基础谷氨酸水平，而对伏隔核 DA 水平没有影响。只有自我给药可卡因的大鼠在两个检查的脑结构中都有基础 GABA 溢出增加。主动或被动可卡因给药增加了伏隔核外源性 DA，但自我给药可卡因的大鼠中可卡因诱发的 DA 水平升高幅度明显更高，而两组动物的伏隔核 GABA 水平也降低。在消退训练的第 10 天，之前给予可卡因的大鼠显示伏隔核内谷氨酸的基础浓度降低，而基础 GABA 水平与盐水对偶对照的基线相比显著增强。钾去极化延迟了主动和被动可卡因组伏隔核和苍白球细胞外谷氨酸水平的降低。目前的数据表明，维持阶段 DA 和 GABA 神经递质传递的变化反映了可卡因摄入的动机方面。根据急性（24 小时）或晚期（10 天）可卡因戒断，不同的神经递质系统（即谷氨酸或 GABA）似乎都参与其中。
