Li Chen, Frantz Kyle J
Neuroscience Institute, Georgia State University, PO Box 5030, Atlanta, GA 30302-5030, United States.
Neuroscience Institute, Georgia State University, PO Box 5030, Atlanta, GA 30302-5030, United States.
Pharmacol Biochem Behav. 2017 Jul;158:49-56. doi: 10.1016/j.pbb.2017.06.003. Epub 2017 Jun 8.
Extinction responding and cue-induced reinstatement of cocaine seeking after 60-days of forced abstinence are attenuated in male rats that self-administered cocaine during adolescence, compared with adults. Given that environmental enrichment during abstinence decreases reinstatement among adults, a possible explanation for attenuated reinstatement among adolescents is that standard pair-housing in prior studies creates a more stimulating environment for younger rats.
Therefore, we tested whether standard pair-housing is necessary for the attenuated reinstatement among adolescents by determining whether an impoverished environment during abstinence would increase reinstatement among adolescents, up to adult levels. Conversely, we also tested whether environmental enrichment could further decrease reinstatement among adolescents, and whether we could replicate effects of environmental enrichment to decrease reinstatement among adults down to adolescent levels (positive controls).
Adolescent and adult male Wistar rats self-administered cocaine intravenously for 12days (fixed ratio 1; 0.36mg/kg per infusion; 2h sessions). Rats were then moved into enriched (grouped, large cages, novel toys), standard (pair-housed, shoebox cages), or impoverished (isolated, hanging cages) housing conditions. After 60days, extinction and cue-induced reinstatement of cocaine seeking were tested, followed by drug-primed reinstatement (0, 5, 10mg/kg cocaine, i.p.).
Consistent with previous results, extinction and cue-induced reinstatement were attenuated in adolescent-onset groups compared with adults; this age difference also extended to drug-primed reinstatement. In support of the present hypothesis, an impoverished environment during abstinence increased reinstatement among adolescents to levels that were not different from adult standard-housing levels.
These data suggest that abstinence environment influences the enduring effects of cocaine among adolescents as well as adults.
与成年雄性大鼠相比，在青春期自行注射可卡因的雄性大鼠在强制戒断60天后，消退反应以及线索诱导的可卡因觅求恢复均有所减弱。鉴于戒断期间的环境丰富化会降低成年大鼠的恢复，青少年恢复减弱的一个可能解释是，先前研究中的标准成对饲养为年幼大鼠创造了一个更具刺激性的环境。
因此，我们通过确定戒断期间的贫困环境是否会使青少年的恢复增加至成年水平，来测试标准成对饲养对于青少年恢复减弱是否必要。相反，我们还测试了环境丰富化是否会进一步降低青少年的恢复，以及我们是否能够复制环境丰富化的效果，将成年大鼠的恢复降低至青少年水平（阳性对照）。
青春期和成年雄性Wistar大鼠静脉注射可卡因12天（固定比率1；每次注射0.36mg/kg；每次注射持续2小时）。然后将大鼠转移到丰富环境（群居、大笼子、新奇玩具）、标准环境（成对饲养、鞋盒笼子）或贫困环境（单独饲养、悬挂笼子）中。60天后，测试可卡因觅求的消退和线索诱导恢复，随后进行药物激发恢复（0、5、10mg/kg可卡因，腹腔注射）。
与先前结果一致，与成年组相比，青春期开始组的消退和线索诱导恢复减弱；这种年龄差异也扩展到药物激发恢复。支持当前假设的是，戒断期间的贫困环境使青少年的恢复增加至与成年标准饲养水平无异的水平。
这些数据表明，戒断环境会影响可卡因对青少年和成年大鼠的持久影响。
