Differential Roles of Oxytocin Receptors in the Prefrontal Cortex and Nucleus Accumbens on Cocaine Self-Administration and Reinstatement of Cued Cocaine Seeking in Male Rats.
Differential Roles of Oxytocin Receptors in the Prefrontal Cortex and Nucleus Accumbens on Cocaine Self-Administration and Reinstatement of Cued Cocaine Seeking in Male Rats.
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DOI：
10.1093/ijnp/pyad059
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发表时间：
2023-12-18
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影响因子：
--
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关于皮质和丘脑催产素受体在药物使用障碍中的具体作用知之甚少。为了更好地理解内源性催产素系统在可卡因复吸行为中的重要性，我们开发了一种腺相关病毒载体表达短发夹（sh）RNA，以选择性地降解大鼠催产素受体（OxyR）mRNA。雄性（Sprague-Dawley）大鼠接受催产素受体的shRNA（shOxyR）或shRNA对照病毒到前额叶皮质（PFC）或丘脑核核心（NAc）中的双侧输注。大鼠自我管理的可卡因在一个不断上升的FR比率为14天，杠杆反应被扑灭，和大鼠进行了测试的线索和可卡因引发的药物寻求恢复。OxyR敲低PFC延迟收购杠杆按固定比例1时间表的强化。所有的老鼠最终都获得了相同水平的杠杆按压和辨别能力，并且在灭绝方面没有差异。OxyR敲低在NAc中没有影响。在PFC和NAc中，shOxyR相对于shRNA对照病毒降低了提示恢复，但在药物引发的恢复期间没有效果。OxyR敲低PFC增加室活动在社会互动任务。这项研究提供了关于内源性OxyRs如何影响药物寻求的关键新信息，以响应不同的复发沉淀物。开发用于敲除大鼠OxyRs的工具可以提供重要的新见解，有助于开发基于催产素的治疗方法，以减少物质使用障碍和其他神经精神疾病患者的复发事件。
Little is known about the specific roles of cortical and accumbal oxytocin receptors in drug use disorders. To better understand the importance of the endogenous oxytocin system in cocaine relapse behavior, we developed an adeno-associated viral vector–expressing short hairpin (sh) RNAs to selectively degrade the rat oxytocin receptor (OxyR) mRNA in vivo. Male (Sprague-Dawley) rats received bilateral infusions of the shRNA for the oxytocin receptor (shOxyR) or an shRNA control virus into the prefrontal cortex (PFC) or the nucleus accumbens core (NAc). Rats self-administered cocaine on an escalating FR ratio for 14 days, lever responding was extinguished, and rats were tested for cued and cocaine-primed reinstatement of drug seeking. OxyR knockdown in the PFC delayed the acquisition of lever pressing on an fixed ratio 1 schedule of reinforcement. All rats eventually acquired the same level of lever pressing and discrimination, and there were no differences in extinction. OxyR knockdown in the NAc had no effect during acquisition. In both the PFC and NAc, the shOxyR decreased cued reinstatement relative to shRNA control virus but was without effect during drug-primed reinstatement. OxyR knockdown in the PFC increased chamber activity during a social interaction task. This study provides critical new information about how endogenous OxyRs function to affect drug seeking in response to different precipitators of relapse. The tool developed to knockdown OxyRs in rat could provide important new insights that aid development of oxytocin-based therapeutics to reduce return-to-use episodes in people with substance use disorder and other neuropsychiatric disorders.
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影响因子：
3.4
作者：
Georgiou, Polymnia;Zanos, Panos;Bailey, Alexis
通讯作者：
Bailey, Alexis
影响因子：
3.7
作者：
Jang, Minji;Jung, Taesub;Noh, Jihyun
通讯作者：
Noh, Jihyun
DOI：
10.1093/ijnp/pyx058
发表时间：
2017-10-01
期刊：
The international journal of neuropsychopharmacology
影响因子：
--
作者：
Leong KC;Freeman LR;Berini CR;Ghee SM;See RE;Reichel CM
通讯作者：
Reichel CM
影响因子：
10.6
作者：
Cox BM;Bentzley BS;Regen-Tuero H;See RE;Reichel CM;Aston-Jones G
通讯作者：
Aston-Jones G
影响因子：
3.4
作者：
Fan, Xin-Yu;Yang, Jing-Yu;Wu, Chun-Fu
通讯作者：
Wu, Chun-Fu