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让青春期大鼠长期接触尼古丁后对尼古丁自我给药行为的习得。

Acquisition of nicotine self-administration in adolescent rats given prolonged access to the drug.

作者信息

Chen Hao, Matta Shannon G, Sharp Burt M

机构信息

Department of Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.

出版信息

Neuropsychopharmacology. 2007 Mar;32(3):700-9. doi: 10.1038/sj.npp.1301135. Epub 2006 Jun 14.

Abstract

As most human tobacco use begins during adolescence and ongoing development of the adolescent central nervous system could affect acquisition of nicotine self-administration (SA), our established rat SA procedure was modified to study adolescent acquisition of SA with prolonged access to nicotine (23 h/day). Postnatal age 43-45 female Lewis rats, without prior shaping, conditioning, or food deprivation, were housed in operant chambers equipped with two levers; pressing the active lever triggered an i.v. injection of nicotine. By the 10th day of SA, rats receiving 7.5, 15, 30, or 60 microg/kg/injection nicotine (free base) obtained 23+/-16, 50+/-8, 65+/-8, or 48+/-5 injections (mean+/-SE), respectively. In the 30 microg/kg/injection group, active : inactive ratio was greater than 2 after SA day 4; 92% of injections occurred during the 12-h active (dark) phase of the light cycle. Main effects (analysis of variance) were shown for day and lever (ie active vs inactive) (p<0.001). Adolescent males showed similar dose-dependent nicotine SA. With the increasing workload imposed by raising the fixed ratio (FR), less nicotine was self-administered at FR 5 and 7 compared to FR 1 and 3. In comparison to adult females self-administering 30 microg/kg/injection of nicotine at FR 1, adolescents acquired nicotine SA at an accelerated rate (p<0.05) and received a greater number of injections (p<0.05) by day 10. In conclusion, when given prolonged access to the drug, both female and male adolescent Lewis rats rapidly acquire nicotine SA within the dosage range and FR constraints previously observed in adult Lewis rats. However, adolescent females acquired the behavior more rapidly and attained higher levels of stable nicotine SA than adults.

摘要

由于大多数人开始吸烟是在青春期,而青少年中枢神经系统的持续发育可能会影响尼古丁自我给药(SA)行为的形成,因此我们对已建立的大鼠SA程序进行了修改,以研究青少年在长时间接触尼古丁(每天23小时)情况下对SA行为的形成。出生后43 - 45天的雌性Lewis大鼠,未经预先塑形、条件训练或禁食,饲养在配备两个杠杆的操作性条件反射箱中;按压主动杠杆会触发静脉注射尼古丁。到SA行为形成的第10天,接受7.5、15、30或60微克/千克/注射尼古丁(游离碱)的大鼠分别获得了23±16、50±8、65±8或48±5次注射(平均值±标准误)。在30微克/千克/注射组中,SA行为形成第4天后主动杠杆与非主动杠杆的按压比率大于2;92%的注射发生在光照周期的12小时活动(黑暗)阶段。方差分析显示天数和杠杆(即主动与非主动)有主要效应(p<0.001)。青春期雄性大鼠表现出类似的剂量依赖性尼古丁SA行为。随着固定比率(FR)增加导致工作量增大,与FR 1和3相比,在FR 5和7时自我给药的尼古丁量减少。与成年雌性大鼠在FR 1时自我给药30微克/千克/注射尼古丁相比,青少年大鼠形成尼古丁SA行为的速度更快(p<0.05),到第10天时接受的注射次数更多(p<0.05)。总之,当给予长时间接触药物的机会时,雌性和雄性青少年Lewis大鼠在先前在成年Lewis大鼠中观察到的剂量范围和FR限制内迅速形成尼古丁SA行为。然而,青少年雌性大鼠比成年大鼠更快地形成这种行为,并达到更高水平的稳定尼古丁SA行为。

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