Effects of pituitary adenylate cyclase-activating polypeptide isoforms in nucleus accumbens subregions on ethanol drinking.
Effects of pituitary adenylate cyclase-activating polypeptide isoforms in nucleus accumbens subregions on ethanol drinking.
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DOI：
10.1111/adb.12972
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发表时间：
2021-05
影响因子：
3.4
通讯作者：
Barson JR
中科院分区：
文献类型：
--
作者：
Gargiulo AT;Pirino BE;Curtis GR;Barson JR
虽然有限的研究已经暗示神经肽，垂体腺苷酸环化酶激活多肽（PACAP），在有问题的酒精使用中，参与这种影响的大脑区域和同型异构体仍有待确定。有一个区域被发现既能与PACAP结合，又能单独参与酒精饮用，那就是伏隔核（NAc）。因此，本研究试图在雄性和雌性Long-Evans大鼠的间歇获取两瓶选择范式下，表征NAc中PACAP异构体对乙醇饮用的影响。将PACAP-27显微注射到NAc内侧外壳中，发现PACAP-27而不是PACAP-38具有剂量依赖性，可以减少酗酒样的酒精饮用。相比之下，PACAP受体拮抗剂PACAP(6-27)，而不是PACAP(6-38)，增强了乙醇饮用。PACAP的这种作用是物质特异性的，因为NAc壳中的同型异构体都不会影响暴饮暴食的蔗糖。这也是解剖特异性的，当PACAP-38而不是PACAP-27注射到NAc核心时，抑制了乙醇的饮用，而PACAP-27注射到NAc内侧壳的尾侧三分之一时，反而增强了饮酒。最后，NAc壳中的PACAP-38影响应力相关的探索行为，减少在光暗箱的光室中花费的时间，PACAP-27对光暗箱或开阔场地的行为没有显著影响。综上所述，这些结果表明，NAc壳中的PACAP-27在不影响特定的应激相关行为的情况下，减弱了酗酒样的酒精饮用，这表明与PACAP亚型相关的化合物应该作为治疗酒精使用障碍的潜在新疗法进行研究。
While limited research has implicated the neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), in problematic alcohol use, the brain regions and isoforms involved in this effect remain to be determined. One region that has been found both to exhibit PACAP binding and, separately, to be involved in ethanol drinking is the nucleus accumbens (NAc). Thus, this study sought to characterize the effect of the PACAP isoforms in the NAc on ethanol drinking under the intermittent-access two-bottle-choice paradigm, in male and female Long-Evans rats. With microinjection into the medial NAc shell, PACAP-27 but not PACAP-38 was found to dose-dependently reduce binge-like ethanol drinking. In contrast, the PACAP receptor antagonist, PACAP (6-27), but not PACAP (6-38), enhanced ethanol drinking. This effect of PACAP was substance-specific, as neither isoform in the NAc shell affected binge-like sucrose drinking. It was also anatomically-specific, as PACAP-38 rather than PACAP-27 suppressed ethanol drinking when injected into the NAc core, and PACAP-27 instead enhanced drinking when injected into the caudal third of the medial NAc shell. Finally, while PACAP-38 in the NAc shell affected stress-related exploratory behavior, reducing time spent in the light chamber of a light-dark box, PACAP-27 did not significantly affect behavior in a light-dark box or open field. Together, these results, showing that PACAP-27 in the NAc shell attenuates binge-like ethanol drinking without affecting select stress-related behaviors, suggest that compounds related to this PACAP isoform should be investigated as potential novel therapeutics for the treatment of alcohol use disorder.
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DOI：
10.1111/acer.13826
发表时间：
2018-09
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Gupta A;Gargiulo AT;Curtis GR;Badve PS;Pandey S;Barson JR
通讯作者：
Barson JR
影响因子：
2.8
作者：
Kovanen, Leena;Saarikoski, Sirkku T.;Partonen, Timo
通讯作者：
Partonen, Timo
影响因子：
3.3
作者：
Gaszner, B.;Kormos, V.;Helyes, Z.
通讯作者：
Helyes, Z.
影响因子：
10.6
作者：
Donahue, Rachel J.;Venkataraman, Archana;Carlezon, William A., Jr.
通讯作者：
Carlezon, William A., Jr.
影响因子：
25
作者：
Calhoon GG;Tye KM
通讯作者：
Tye KM