Alcohol consumption modulates prelimbic cortex response to cocaine following sequential cocaine and alcohol polysubstance use in the rat.
Alcohol consumption modulates prelimbic cortex response to cocaine following sequential cocaine and alcohol polysubstance use in the rat.
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DOI：
10.3389/fphar.2023.1132689
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发表时间：
2023
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
多物质使用（PSU）指在一段时间内使用一种以上的药物，在可卡因使用者中很普遍。头孢曲松（Ceftriaxone）是一种β -内酰胺类抗生素，在临床前模型中，通过恢复可卡因自我给药后的谷氨酸稳态，可靠地减轻了可卡因寻求的恢复，但当大鼠同时摄入可卡因和酒精（可卡因+酒精PSU）时，这种作用就失效了。我们之前发现，可卡因+酒精PSU大鼠恢复可卡因寻求与仅可卡因大鼠相似，但在整个奖励系统中表现出恢复诱导的c-Fos表达的差异，包括头孢曲松治疗后缺乏变化。在这里，我们使用这个模型来确定先前的发现是由对可卡因药理作用的耐受性还是致敏性引起的。在连续12天的时间里，雄性大鼠先接受静脉注射可卡因，然后在笼子里饮水或无糖酒精6小时。随后，大鼠进行了每天10次的工具灭绝实验，在此期间，它们分别接受了载药或头孢曲松治疗。然后大鼠接受非偶然的可卡因注射，并灌注用于稍后免疫组织化学分析c-Fos在奖励神经回路中的表达。PSU大鼠前边缘皮层c-Fos表达与总酒精摄入量相关。头孢曲松和PSU对边缘下皮层、伏隔核核和壳、杏仁核基底外侧和腹侧被盖区c-Fos表达均无影响。这些结果支持了PSU和头孢曲松在缺乏药物耐受性或对可卡因敏感的情况下改变潜在药物寻求行为的神经生物学的观点。
Polysubstance use (PSU), involves the consumption of more than one drug within a period of time and is prevalent among cocaine users. Ceftriaxone, a beta-lactam antibiotic, reliably attenuates reinstatement of cocaine seeking in pre-clinical models by restoring glutamate homeostasis following cocaine self-administration but fails to do so when rats consume both cocaine and alcohol (cocaine + alcohol PSU). We previously found that cocaine + alcohol PSU rats reinstate cocaine seeking similarly to cocaine-only rats, but demonstrate differences in reinstatement-induced c-Fos expression throughout the reward system, including a lack of change upon ceftriaxone treatment. Here, we used this model to determine if previous findings were caused by tolerance or sensitization to the pharmacological effects of cocaine. Male rats underwent intravenous cocaine self-administration immediately followed by 6 h of home cage access to water or unsweetened alcohol for 12 days. Rats subsequently underwent 10 daily instrumental extinction sessions, during which time they were treated with either vehicle or ceftriaxone. Rats then received a non-contingent cocaine injection and were perfused for later immunohistochemical analysis of c-Fos expression in the reward neurocircuitry. c-Fos expression in the prelimbic cortex correlated with total alcohol intake in PSU rats. There were no effects of either ceftriaxone or PSU on c-Fos expression in the infralimbic cortex, nucleus accumbens core and shell, basolateral amygdala, or ventral tegmental area. These results support the idea that PSU and ceftriaxone alter the neurobiology underlying drug-seeking behavior in the absence of pharmacological tolerance or sensitization to cocaine.
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影响因子：
16.2
作者：
Hearing M;Kotecki L;Marron Fernandez de Velasco E;Fajardo-Serrano A;Chung HJ;Luján R;Wickman K
通讯作者：
Wickman K
DOI：
10.1523/jneurosci.2277-12.2012
发表时间：
2012-09-19
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Mahler SV;Aston-Jones GS
通讯作者：
Aston-Jones GS
影响因子：
7.6
作者：
Griffin, William C., III;Haun, Harold L.;Becker, Howard C.
通讯作者：
Becker, Howard C.
影响因子：
3.4
作者：
McLaughlin, J;See, RE
通讯作者：
See, RE
影响因子：
3.3
作者：
Kedia, Satish;Sell, Marie A.;Relyea, George
通讯作者：
Relyea, George