Pituitary adenylate cyclase-activating polypeptide type 1 receptor within the nucleus accumbens core mediates excessive alcohol drinking in alcohol-preferring rats.
Pituitary adenylate cyclase-activating polypeptide type 1 receptor within the nucleus accumbens core mediates excessive alcohol drinking in alcohol-preferring rats.
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延髓核核心内的腺苷酸环化酶激活多肽1型受体介导嗜酒大鼠过量饮酒。
DOI：
10.1016/j.neuropharm.2022.109063
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发表时间：
2022-07-01
影响因子：
4.7
通讯作者：
Sabino, Valentina
中科院分区：
文献类型：
--
作者：
Minnig, Margaret A.;Blasio, Angelo;Ferragud, Antonio;Sami, Yasmine N.;Erhard, Emily E.;Clark, Rose H.;DiLeo, Alyssa;Giuliano, Chiara;Everitt, Barry J.;Cottone, Pietro;Sabino, Valentina
酒精使用障碍（AUD）具有很强的遗传性;然而，介导过量饮酒倾向的神经生物学机制仍不清楚。腺苷酸环化酶激活多肽（PACAP）是一种高度保守的神经肽，主要通过PAC 1受体（PAC 1 R）发挥作用，被认为是药物滥用和酒精作用的介质之一。在这里，我们研究了PACAP/PAC 1 R系统在酒精偏好大鼠（一种已建立的AUD动物模型）过度饮酒中的作用。脑室内（i. c. v.）PAC 1 R拮抗剂PACAP（6-38）的给药阻断了Sardinian酒精偏好（Scr：sP）大鼠的过度饮酒和饮酒动机，而不影响水、糖精或蔗糖的摄入。值得注意的是，PACAP（6-38）不影响远系Wistar大鼠的乙醇反应。PACAP（6-38）也显著减少了二阶强化计划下的酒精寻求行为。使用免疫组织化学，PAC 1 R阳性细胞的数量显着增加，观察到选择性的核脑桥（NAcc）核心的Scr：sP大鼠，相比，Wistar大鼠，饮酒。最后，Scr：sP大鼠的过量饮酒受到NAcc核心内（而非NAcc外壳内）PACAP（6-38）以及NAcc核心中病毒介导的PAC 1 R敲低的抑制。目前的研究表明，PACAP/PAC 1 R系统的过度活跃，特别是在NAcc核心介导过度饮酒的酒精偏好大鼠，并表明该系统可能代表一个新的目标，为治疗AUD。
Alcohol use disorders (AUD) have a strong component of heritability; however, the neurobiological mechanisms mediating the propensity to consume excessive amounts of alcohol are still not well understood. Pituitary adenylate cyclase-activating polypeptide (PACAP), a highly conserved neuropeptide which exerts its effects mainly through the PAC1 receptor (PAC1R), has been suggested to be one of the mediators of the effects of drugs of abuse and alcohol. Here, we investigated the role of the PACAP/PAC1R system in excessive alcohol drinking in alcohol-preferring rats, an established animal model of AUD. Intracerebroventricular (i.c.v.) administration of the PAC1R antagonist PACAP(6–38) blocked excessive alcohol drinking and motivation to drink in Sardinian alcohol-preferring (Scr:sP) rats, without affecting water, saccharin, or sucrose intake. Notably, PACAP(6–38) did not affect ethanol responding in outbred Wistar rats. PACAP(6–38) also significantly reduced alcohol-seeking behavior under a second-order schedule of reinforcement. Using immunohistochemistry, a significant increase in the number of PAC1R positive cells was observed selectively in the nucleus accumbens (NAcc) Core of Scr:sP rats, compared to Wistar rats, following alcohol drinking. Finally, excessive drinking in Scr: sP rats was suppressed by intra-NAcc Core, but not intra-NAcc Shell, PACAP(6–38), as well as by virally-mediated PAC1R knockdown in the NAcc Core. The present study shows that hyperactivity of the PACAP/PAC1R system specifically in the NAcc Core mediates excessive drinking of alcohol-preferring rats, and indicates that this system may represent a novel target for the treatment of AUD.
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影响因子：
7.6
作者：
Dore, Riccardo;Iemolo, Attilio;Sabino, Valentina
通讯作者：
Sabino, Valentina
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QUINN, WG