Role of prefrontal cortex projections to the nucleus accumbens core in mediating the effects of ceftriaxone on cue-induced cocaine seeking.
Role of prefrontal cortex projections to the nucleus accumbens core in mediating the effects of ceftriaxone on cue-induced cocaine seeking.
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前额叶皮层对伏隔核核心核心的作用在介导头孢曲松对提示引起的可卡因寻求的影响中的作用。
DOI：
10.1111/adb.12928
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发表时间：
2021-03
影响因子：
3.4
通讯作者：
Knackstedt LA
中科院分区：
文献类型：
--
作者：
Bechard AR;Logan CN;Mesa J;Padovan-Hernandez Y;Blount H;Hodges VL;Knackstedt LA
头孢曲松是一种抗生素，它可以可靠地减弱可卡因消失后的恢复，同时防止驱动恢复的伏隔核谷氨酸外排。然而，当大鼠经历无灭绝的戒断时，头孢曲松减弱了情境启动的可卡因寻求，但NA核心谷氨酸外排仍然增加。在这里，我们试图确定在可卡因戒断后，当可卡因寻求同时受到情境和离散线索（线索诱导寻求）的提示时，是否会发生同样的情况。雄性大鼠自我静脉注射可卡因，并伴有药物相关提示（浅色+音调），每天2小时，连续14天。然后，在两周的时间里，大鼠经历了每天处理的禁欲训练，但没有灭绝训练。在最后6天戒断期间给予头孢曲松（200 mg/kg IP）或对照药。在线索诱导的可卡因寻找测试中，进行了微透析程序。大鼠在实验结束时灌注供后期Fos分析。另一组大鼠在NA核心注入逆行示踪剂霍乱毒素B，并进行相同的自我给药和复发程序。在这项试验中，头孢曲松增加了基线谷氨酸，减弱了线索诱导的可卡因寻找和NA核心谷氨酸外排。头孢曲松降低了向NA核发送投射的区域（前额皮质、基底外侧杏仁核、腹侧被盖区）的Fos表达，并特别降低了向NA核发送投射的前边缘皮质而非边缘下皮质神经元的Fos表达。因此，当可卡因寻求被药物相关线索诱导时，头孢曲松能够通过防止NA核谷氨酸外排来减轻复发，这可能是通过降低边缘前NA核投射神经元的活性。
Ceftriaxone is an antibiotic that reliably attenuates the reinstatement of cocaine seeking after extinction while preventing the nucleus accumbens (NA) core glutamate efflux that drives reinstatement. However, when rats undergo abstinence without extinction, ceftriaxone attenuates context-primed cocaine seeking but NA core glutamate efflux still increases. Here we sought to determine if the same would occur when cocaine seeking is prompted by both context and discrete cues (cue-induced seeking) after cocaine abstinence. Male rats self-administered intravenous cocaine accompanied by drug-associated cues (light+tone) for 2 hr/day for 14 days. Rats then experienced abstinence with daily handling but no extinction training for two weeks. Ceftriaxone (200 mg/kg IP) or vehicle was administered during the last 6 days of abstinence. During a cue-induced cocaine seeking test, microdialysis procedures were conducted. Rats were perfused at the end of the test for later Fos analysis. A separate cohort of rats was infused with the retrograde tracer cholera toxin B in the NA core and underwent the same self-administration and relapse procedures. Ceftriaxone increased baseline glutamate and attenuated both cue-induced cocaine seeking and NA core glutamate efflux during this test. Ceftriaxone reduced Fos expression in regions sending projections to the NA core (prefrontal cortex, basolateral amygdala, ventral tegmental area) and specifically reduced Fos in prelimbic cortex and not infralimbic cortex neurons projecting to the NA core. Thus, when cocaine seeking is induced by drug-associated cues, ceftriaxone is able to attenuate relapse by preventing NA core glutamate efflux, likely through reducing activity in prelimbic NA core-projecting neurons.
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影响因子：
25
作者：
Bock, Roland;Shin, J. Hoon;Kaplan, Alanna R.;Dobi, Alice;Markey, Eric;Kramer, Paul F.;Gremel, Christina M.;Christensen, Christine H.;Adrover, Martin F.;Alvarez, Veronica A.
通讯作者：
Alvarez, Veronica A.
影响因子：
16.2
作者：
Cameron, Courtney M.;Murugan, Malavika;Witten, Ilana B.
通讯作者：
Witten, Ilana B.
影响因子：
5.3
作者：
Augur, Isabel F.;Wyckoff, Andrew R.;Peters, Jamie
通讯作者：
Peters, Jamie
影响因子：
4.2
作者：
Ball, Kevin T.;Stone, Eric;Woodlen, Kristin
通讯作者：
Woodlen, Kristin
影响因子：
5.3
作者：
Guzman, Daniel;Carreira, Maria B.;Self, David W.
通讯作者：
Self, David W.