Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA; Paul and Carole Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA; Paul and Carole Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
Peptides. 2020 Dec;134:170403. doi: 10.1016/j.peptides.2020.170403. Epub 2020 Aug 31.
Atrial Naturietic Peptide (ANP) is a neuropeptide that regulates function of the hypothalamic-pituitary-adrenal (HPA) axis, immune and neuroimmune system, and epigenetic factors. Research has indicated that ANP may mediate alcohol intake, withdrawal, and craving like behaviors. ANP receptors are present in the mesocorticolimbic (MCL) reward pathway of the brain, which includes the nucleus accumbens (Acb) and the ventral tegmental area (VTA). The objectives of the present study were to examine the effects of ANP microinjected into Acb subregions (Shell (Sh), Core (Co), ventral to AcbSh) on operant ethanol (EtOH) self-administration and into posterior VTA (pVTA) on EtOH-seeking behavior of female alcohol-preferring (P) rats. In the first experiment, ANP (0, 10 μg, or 100 μg) was microinjected into subregions of the Acb to determine its effects on EtOH self-administration. In the second experiment, ANP was microinjected into pVTA to determine its effects on Pavlovian Spontaneous Recovery (PSR) of responding, a measure of context-induced EtOH-seeking behavior. Administration of ANP directly into the AcbSh significantly reduced EtOH self-administration compared to vehicle, whereas ANP into the AcbCo or areas directly ventral to the AcbSh did not alter responding for EtOH. Microinjection of ANP into the pVTA significantly reduced responding on the EtOH-associated lever during the PSR test. The data indicate that activation of ANP systems in the (a) AcbSh can inhibit EtOH intake, and (b) in the pVTA can inhibit EtOH-seeking behavior. The results suggest that manipulations of the ANP system could be a potential target for pharmacotherapeutic intervention to treat alcohol use disorder. Supported in part by AA07462, AA07611, AA10717, AA10721, AA013522, AA019366, AA020908, AA022287, and AA024612.
心房利钠肽（ANP）是一种神经肽，可调节下丘脑-垂体-肾上腺（HPA）轴、免疫和神经免疫以及表观遗传因子的功能。研究表明，ANP 可能介导酒精摄入、戒断和渴望行为。ANP 受体存在于大脑的中脑边缘奖赏通路中，包括伏隔核（Acb）和腹侧被盖区（VTA）。本研究的目的是检查 ANP 微注射到 Acb 亚区（壳（Sh）、核心（Co）、AcbSh 腹侧）对雌性酒精偏好（P）大鼠操作性乙醇（EtOH）自我给药的影响，以及 ANP 微注射到后 VTA（pVTA）对 EtOH 寻求行为的影响。在第一个实验中，将 ANP（0、10μg 或 100μg）微注射到 Acb 的亚区，以确定其对 EtOH 自我给药的影响。在第二个实验中，将 ANP 微注射到 pVTA，以确定其对 Pavlovian Spontaneous Recovery（PSR）反应的影响，PSR 是衡量与环境相关的 EtOH 寻求行为的指标。与载体相比，直接将 ANP 注射到 AcbSh 中可显著减少 EtOH 自我给药，而将 ANP 注射到 AcbCo 或直接位于 AcbSh 腹侧的区域不会改变 EtOH 的反应。将 ANP 微注射到 pVTA 可显著减少 PSR 测试中与 EtOH 相关的 lever 的反应。数据表明，激活（a）AcbSh 中的 ANP 系统可以抑制 EtOH 摄入，（b）在 pVTA 中可以抑制 EtOH 寻求行为。结果表明，ANP 系统的操作可以成为治疗酒精使用障碍的潜在药物治疗靶点。部分得到 AA07462、AA07611、AA10717、AA10721、AA013522、AA019366、AA020908、AA022287 和 AA024612 的支持。
