Miguéns M, Del Olmo N, Higuera-Matas A, Torres I, García-Lecumberri C, Ambrosio E
Departamento de Psicobiología, Facultad de Psicología, UNED, C/ Juan del Rosal no. 10, 28040 Madrid, Spain.
Psychopharmacology (Berl). 2008 Feb;196(2):303-13. doi: 10.1007/s00213-007-0958-x. Epub 2007 Oct 17.
Accumbal excitatory amino acid (EAA) transmission has been implicated in cocaine addiction. However, the time course effects of extinction of cocaine self-administration on EAAs are unknown.
The objective of this study was to define the time course of cocaine self-administration and extinction effects on glutamate and aspartate levels in the nucleus accumbens.
Rats were trained to self-administer cocaine for 20 days, and the levels of extracellular glutamate and aspartate were measured by in vivo microdialysis both during cocaine self-administration and after a priming cocaine injection at different time points after extinction (1, 5, or 10 days). A food-reinforced control group was also included in this study. Furthermore, the effect of acute i.v. cocaine administration (0, 1, 2, or 4 mg/kg) on glutamate and aspartate levels was also evaluated.
At any of the dose tested, acute i.v. cocaine did not affect the levels of glutamate or aspartate in the Nacc. In contrast, glutamate levels were reduced in animals trained to self-administer cocaine, although they augmented substantially during a subsequent session of cocaine self-administration, and similar changes were not observed in food-reinforced controls. After 1 or 5, but not after 10 days of extinction, the glutamate levels were also reduced, and the ability of i.v. cocaine priming injections to increase glutamate levels followed a similar time course. These effects were specific, as aspartate levels were not affected by any administration protocol.
These data suggest that glutamatergic transmission could be involved in the maintenance of cocaine self-administration and in the early phases of abstinence.
伏隔核兴奋性氨基酸（EAA）传递与可卡因成瘾有关。然而，可卡因自我给药消退对EAA的时间进程影响尚不清楚。
本研究的目的是确定可卡因自我给药及其消退对伏隔核中谷氨酸和天冬氨酸水平的时间进程影响。
训练大鼠自我给药可卡因20天，并在可卡因自我给药期间以及消退后不同时间点（1、5或10天）进行一次可卡因激发注射后，通过体内微透析测量细胞外谷氨酸和天冬氨酸水平。本研究还包括一个食物强化对照组。此外，还评估了急性静脉注射可卡因（0、1、2或4mg/kg）对谷氨酸和天冬氨酸水平的影响。
在任何测试剂量下，急性静脉注射可卡因均未影响伏隔核中谷氨酸或天冬氨酸水平。相反，训练自我给药可卡因的动物中谷氨酸水平降低，尽管在随后的可卡因自我给药过程中显著升高，而在食物强化对照组中未观察到类似变化。在消退1天或5天后，但不是10天后，谷氨酸水平也降低，静脉注射可卡因激发注射增加谷氨酸水平的能力遵循类似的时间进程。这些影响是特异性的，因为任何给药方案均未影响天冬氨酸水平。
这些数据表明，谷氨酸能传递可能参与可卡因自我给药的维持以及戒断的早期阶段。
