Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health/Department of Health and Human Services, Bethesda, Maryland 20892, USA.
J Neurosci. 2013 May 22;33(21):9050-5. doi: 10.1523/JNEUROSCI.0503-13.2013.
While glutamate in the nucleus accumbens (NAS) contributes to the promotion of drug-seeking by drug-predictive cues, it also appears to play a role in the inhibition of drug-seeking following extinction procedures. Thus we measured extracellular fluctuations of NAS glutamate in response to discriminative stimuli that signaled either cocaine availability or cocaine omission. We trained rats to self-administer intravenous cocaine and then to recognize discriminative odor cues that predicted either sessions where cocaine was available or alternating sessions where it was not (saline substituted for cocaine). Whereas responding in cocaine availability sessions remained stable, responding in cocaine omission sessions progressively declined to chance levels. We then determined the effects of each odor cue on extracellular glutamate in the core and shell subregions of NAS preceding and accompanying lever pressing under an extinction condition. Glutamate levels were elevated in both core and shell by the availability odor and depressed in the core but not the shell by the omission odor. Infusion of kynurenic acid (an antagonist for ionotropic glutamate receptors) into core but not shell suppressed responding associated with the availability odor, but had no effect on the suppression associated with the omission odor. Thus cocaine-predictive cues appear to promote cocaine seeking in part by elevating glutamatergic neurotransmission in the core of NAS, whereas cocaine-omission cues appear to suppress cocaine seeking in part by depressing glutamatergic receptor activation in the same region.
虽然伏隔核（NAS）中的谷氨酸有助于促进药物预测线索引发的觅药行为，但它似乎也在消退程序后抑制觅药行为中发挥作用。因此，我们测量了 NAS 谷氨酸在外显刺激下的细胞外波动，这些刺激信号表示可卡因的可用性或可卡因的缺失。我们训练大鼠进行静脉内可卡因自我给药，然后识别预测可卡因可用或交替的可卡因缺失（盐水替代可卡因）的辨别气味线索。虽然在可卡因可用的时间段内的反应保持稳定，但在可卡因缺失的时间段内的反应逐渐下降到随机水平。然后，我们在消退条件下，在核心和壳区 NAS 的前导和伴随杠杆按压之前和期间，确定每个气味线索对核心和壳区 NAS 细胞外谷氨酸的影响。可用性气味会升高核心和壳区的谷氨酸水平，而缺失气味会降低核心区但不会降低壳区的谷氨酸水平。将犬尿氨酸（离子型谷氨酸受体拮抗剂）注入核心区而非壳区会抑制与可用性气味相关的反应，但对与缺失气味相关的抑制无影响。因此，可卡因预测线索似乎通过增加 NAS 核心区的谷氨酸能神经传递来促进可卡因觅药，而可卡因缺失线索似乎通过抑制同一区域的谷氨酸能受体激活来抑制可卡因觅药。
