A Role For The Prefrontal Cortex In Heroin-Seeking After Forced Abstinence By Adult Male Rats But Not Adolescents
A Role For The Prefrontal Cortex In Heroin-Seeking After Forced Abstinence By Adult Male Rats But Not Adolescents
复制标题
DOI：
10.1038/npp.2012.200
复制
发表时间：
2013-02-01
影响因子：
7.6
通讯作者：
Frantz, Kyle J.
中科院分区：
文献类型：
--
作者：
Doherty, James M.;Cooke, Bradley M.;Frantz, Kyle J.
据推测，青少年滥用药物会增加吸毒成瘾的风险。然而，与成年鼠相比，青少年时期自我服用海洛因的雄性大鼠在戒断后表现出较少的药物寻求。本研究探讨了内侧前额叶皮层（mPFC）的神经活动在年龄依赖性海洛因寻求中的作用。青少年雄性大鼠（35日龄）和成年雄性大鼠（86日龄）采用固定比例1强化方案（每次注射0.05和0.025 mg/kg）获得海洛因维持的杠杆按压。在强制戒断12天后，通过测量主动杠杆上的杠杆按压次数，在1小时内对大鼠进行海洛因寻求测试。然后使用无偏立体学来估计边缘前和边缘下mPFC中Fos-ir（+）和Fos-ir（-）神经元的数量。和之前一样，青少年和成年自我施用的海洛因数量相似，但随后在年轻的大鼠中寻求海洛因的情况有所减少。同样，在海洛因寻找测试中，青少年组在边缘前或边缘下的mPFC中没有显示出显著的神经激活，而成年海洛因自我给药组在两个mPFC亚区显示出比盐水组多2到6倍的Fos-ir（+）神经元。最后，青少年发病组的大鼠边缘下皮层的神经元总数比成年大鼠要多。因此，mPFC可能在海洛因自我服用的一些年龄依赖性效应中起关键作用。神经精神药理学（2013）38,446-454；doi: 10.1038 / npp.2012.200;2012年10月17日在线发布
Adolescent drug abuse is hypothesized to increase the risk of drug addiction. Yet male rats that self-administer heroin as adolescents show attenuated drug-seeking after abstinence, compared with adults. Here we explore a role for neural activity in the medial prefrontal cortex (mPFC) in age-dependent heroin-seeking. Adolescent (35-day-old at start; adolescent-onset) and adult (86-day-old at start) male rats acquired lever-pressing maintained by heroin using a fixed ratio one reinforcement schedule (0.05 and 0.025 mg/kg per infusion). Following 12 days of forced abstinence, rats were tested for heroin-seeking over 1 h by measuring the number of lever presses on the active lever. Unbiased stereology was then used to estimate the number of Fos-ir(+) and Fos-ir(-) neurons in prelimbic and infralimbic mPFC. As before, adolescents and adults self-administered similar amounts of heroin, but subsequent heroin-seeking was attenuated in the younger rats. Similarly, the adolescent-onset group failed to show significant neural activation in the prelimbic or infralimbic mPFC during the heroin-seeking test, whereas the adult-onset heroin self-administration group showed two to six times more Fos-ir(+) neurons than their saline counterparts in both mPFC subregions. Finally, the overall number of neurons in the infralimbic cortex was greater in rats from the adolescent-onset groups than adults. The mPFC may thus have a key role in some age-dependent effects of heroin self-administration. Neuropsychopharmacology (2013) 38, 446-454; doi:10.1038/npp.2012.200; published online 17 October 2012