Enduring Loss of Serotonergic Control of Orbitofrontal Cortex Function Following Contingent and Noncontingent Cocaine Exposure.
Enduring Loss of Serotonergic Control of Orbitofrontal Cortex Function Following Contingent and Noncontingent Cocaine Exposure.
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偶然和非偶然接触可卡因后，眶额皮质功能的血清素控制持续丧失。
DOI：
10.1093/cercor/bhw312
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Lupica,CarlR
中科院分区：
文献类型：
--
作者：
Wright,AndrewM;Zapata,Agustin;Baumann,MichaelH;Elmore,JoshuaS;Hoffman,AlexanderF;Lupica,CarlR
Clinical descriptions of cocaine addiction include compulsive drug seeking and maladaptive decision-making despite substantial aversive consequences. Research suggests that this may result from altered orbitofrontal cortex (OFC) function and its participation in outcome-based behavior. Clinical and animal studies also implicate serotonin in the regulation of OFC function in addiction and other neuropsychiatric disorders. Here we test the hypothesis that exposure to cocaine, through self-administration (CSA) or yoked-administration (CYA), alters the regulation of OFC function by 5-HT. Using whole-cell electrophysiology in brain slices from naïve rats we find that 5-HT1Areceptors generate hyperpolarizing outward currents in layer-V OFC pyramidal neurons, and that 5-HT2Areceptors increase glutamate release onto these cells. Following extended withdrawal from CSA or CYA, this 5-HT regulation of OFC activity is largely lost. In-situ hybridization of 5-HT receptor transcripts reveals that 5-HT1Areceptor mRNA is unaffected and 5-HT2Areceptor mRNA is significantly elevated after CSA or CYA. These results demonstrate that 5-HT control of OFC neurons is disrupted for extended periods following cocaine exposure. We hypothesize that this dysregulation of 5-HT signaling leads to enduring disruptions of OFC network activity that this is involved in impaired decision-making associated with cocaine addiction.
