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重复静脉注射腱生蛋白C末端相关肽(TCAP)-1可减弱促肾上腺皮质激素释放因子(CRF)诱导的大鼠可卡因觅药行为复燃。

Repeated intravenous administrations of teneurin-C terminal associated peptide (TCAP)-1 attenuates reinstatement of cocaine seeking by corticotropin-releasing factor (CRF) in rats.

作者信息

Erb Suzanne, McPhee Matthew, Brown Zenya J, Kupferschmidt David A, Song Lifang, Lovejoy David A

机构信息

Department of Psychology, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada; Department of Cell and Systems Biology, University of Toronto, 1265 Military Trail, Toronto, ON M1C 1A4, Canada.

Department of Psychology, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada.

出版信息

Behav Brain Res. 2014 Aug 1;269:1-5. doi: 10.1016/j.bbr.2014.04.013. Epub 2014 Apr 21.

Abstract

The teneurin c-terminal associated peptides (TCAP) have been implicated in the regulation of the stress response, possibly via a corticotropin-releasing factor (CRF)-related mechanism. We have previously shown that repeated intracerebroventricular (ICV) injections of TCAP-1 attenuate the reinstatement of cocaine seeking by CRF in rats. Here, we determined whether intravenous (IV) administrations of TCAP-1 would likewise attenuate CRF-induced reinstatement, and whether this effect would vary depending on the rat's history of cocaine self administration. Rats were trained to self-administer cocaine for 10 days, during once daily sessions that were either 3h ("short access"; ShA) or 6h ("long access"; LgA). Rats were then given five daily injections of TCAP-1 (0, 300, or 3,000 pmol, IV) in their home cage. Subsequently, they were returned to the self-administration chambers where extinction of cocaine seeking and testing for CRF-induced reinstatement of cocaine seeking was carried out. Repeated IV administrations of TCAP-1 were efficacious in attenuating CRF-induced reinstatement of cocaine seeking, but at different doses in ShA and LgA rats. Taken together, the findings extend previous work showing a consistent effect of repeated ICV TCAP-1 on CRF-induced reinstatement of cocaine seeking, and point to a potential therapeutic benefit of TCAP-1 in attenuating cocaine seeking behaviors.

摘要

腱生蛋白C末端相关肽(TCAP)可能通过一种促肾上腺皮质激素释放因子(CRF)相关机制参与应激反应的调节。我们之前已经表明,重复脑室内(ICV)注射TCAP-1可减弱大鼠中CRF诱导的可卡因觅求行为的恢复。在此,我们确定静脉内(IV)注射TCAP-1是否同样会减弱CRF诱导的恢复,以及这种效应是否会因大鼠的可卡因自我给药史而异。大鼠接受为期10天的可卡因自我给药训练,每天一次,每次给药时长分别为3小时(“短给药时长”;ShA)或6小时(“长给药时长”;LgA)。然后,在大鼠的饲养笼中每天给它们注射五次TCAP-1(0、300或3000皮摩尔,静脉注射)。随后,将它们放回自我给药室,在那里进行可卡因觅求行为的消退测试以及CRF诱导的可卡因觅求行为恢复的测试。重复静脉注射TCAP-1可有效减弱CRF诱导的可卡因觅求行为的恢复,但对ShA和LgA大鼠的有效剂量不同。综上所述,这些发现扩展了先前的研究工作,表明重复脑室内注射TCAP-1对CRF诱导的可卡因觅求行为的恢复具有一致的作用,并指出TCAP-1在减弱可卡因觅求行为方面具有潜在的治疗益处。

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