Endogenous glutamate within the prelimbic and infralimbic cortices regulates the incubation of cocaine-seeking in rats.
Endogenous glutamate within the prelimbic and infralimbic cortices regulates the incubation of cocaine-seeking in rats.
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内核和输液性皮质中的内源性谷氨酸调节大鼠可卡因寻求可卡因的孵化。
DOI：
10.1016/j.neuropharm.2017.10.024
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发表时间：
2018-01
影响因子：
4.7
通讯作者：
Szumlinski KK
中科院分区：
文献类型：
--
作者：
Shin CB;Templeton TJ;Chiu AS;Kim J;Gable ES;Vieira PA;Kippin TE;Szumlinski KK
线索增强的可卡因寻找的潜伏期与腹内侧前额叶皮层（vmPFC）内细胞外谷氨酸的增加相一致。vmPFC由两个相反调节药物寻找的亚区组成，边缘下（IL）活性抑制，边缘前（PL）活性促进药物寻找。因此，我们假设IL内内源性谷氨酸的增加和减少会分别减弱和增强线索增强的药物寻求行为，而在PL内内源性谷氨酸的操作中观察到相反的效果。雄性Sprague-Dawley大鼠被训练为自我服用可卡因（0.25 mg/输注；6小时/天X 10天），其递送通过音调光线索发出信号。然后将大鼠再分为3天和30天的戒断组。实验中，将20 mM的mGlu2/3激动剂LY379268（降低内源性谷氨酸）或300 μM的兴奋性氨基酸转运抑制剂tho -β-苄氧天冬氨酸（TBOA，提高内源性谷氨酸）注入IL或PL （0.5 μl/侧），然后进行30分钟的提示强化寻药试验。灌药大鼠对可卡因相关杠杆表现出孵育反应。LY379268和TBOA在停药3天后都没有改变行为，这表明两个亚区中的谷氨酸都没有调节早期停药时线索强化的觅药行为。停药30 d时，pll内LY379268显微注射显著降低了觅药行为，而il内注射效果较为温和。有趣的是，il内TBOA减弱了长期停药期间的药物寻找，但当注入l内时不影响行为。这些结果表明，在寻求药物的反应中，PL内的谷氨酸释放可能驱动了长期戒断期间潜伏的可卡因寻求的表现。
The incubation of cue-reinforced cocaine-seeking coincides with increased extracellular glutamate within the ventromedial prefrontal cortex (vmPFC). The vmPFC is comprised of two subregions that oppositely regulate drug-seeking, with infralimbic (IL) activity inhibiting, and prelimibic (PL) activity facilitating, drug-seeking. Thus, we hypothesized that increasing and decreasing endogenous glutamate within the IL would attenuate and potentiate, respectively, cue-reinforced drug-seeking behavior, with the converse effects observed upon manipulations of endogenous glutamate within the PL. Male Sprague-Dawley rats were trained to self-administer cocaine (0.25 mg/infusion; 6 h/day X 10 days), the delivery of which was signaled by a tone-light cue. Rats were then subdivided into 3 or 30 day withdrawal groups. For testing, rats were microinjected with vehicle, 20 mM of the mGlu2/3 agonist LY379268 (to lower endogenous glutamate), or 300 μM of the excitatory amino acid transporter inhibitor threo-β-benzyloxyaspartate (TBOA; to raise endogenous glutamate) into either the IL or PL (0.5 μl/side) and then given a 30-min test for cue-reinforced drug-seeking. Vehicle-infused rats exhibited incubated responding on the cocaine-associated lever. Neither LY379268 nor TBOA altered behavior at 3 days withdrawal, indicating that glutamate within neither subregion regulates cue-reinforced drug-seeking during early withdrawal. At 30 days withdrawal, intra-PL LY379268 microinjection significantly decreased drug-seeking behavior, while the effect was more modest when infused intra-IL. Interestingly, intra-IL TBOA attenuated incubated drug-seeking during protracted withdrawal, but did not affect behavior when infused intra-PL. These results argue that glutamate release within the PL in response to drug-seeking likely drives the manifestation of incubated cocaine-seeking during protracted withdrawal.
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影响因子：
2.7
作者：
Dhonnchadha, B. A. Nic;Lovascio, B. F.;Shrestha, N.;Lin, A.;Leite-Morris, K. A.;Man, H. Y.;Kaplan, G. B.;Kantak, K. M.
通讯作者：
Kantak, K. M.
影响因子：
3.4
作者：
Capriles, N;Rodaros, D;Stewart, J
通讯作者：
Stewart, J
影响因子：
3.3
作者：
Hamlin, A. S.;Clemens, K. J.;Mcnally, G. P.
通讯作者：
Mcnally, G. P.
DOI：
10.1523/jneurosci.3278-12.2013
发表时间：
2013-05-29
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Fischer KD;Houston AC;Rebec GV
通讯作者：
Rebec GV
影响因子：
3.4
作者：
Franklin, TR;Druhan, JP
通讯作者：
Druhan, JP