Adolescent rats find repeated Δ9-THC less aversive than adult rats but display greater residual cognitive deficits and changes in hippocampal protein expression following exposure
Adolescent rats find repeated Δ9-THC less aversive than adult rats but display greater residual cognitive deficits and changes in hippocampal protein expression following exposure
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DOI：
10.1038/sj.npp.1301475
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发表时间：
2008-04-01
影响因子：
7.6
通讯作者：
McGregor, Iain S.
中科院分区：
文献类型：
--
作者：
Quinn, Heidi R.;Matsumoto, Izuru;McGregor, Iain S.
目前的研究调查了青春期大鼠是否比成年大鼠更容易受到大麻素暴露对大脑和行为的持久不利影响。雄性Wistar大鼠多次染毒Delta-9-四氢大麻酚(Delta(9)-THC，5 mg/kg ip)。在青春期(出生后28天以上)或成人(出生后60天以上)发育阶段的位置制约范式中。成年大鼠在四次或八次配对后避免了Delta(9)-THC配对的环境，这种回避在最后一次Delta(9)-THC注射后至少持续了16天。相比之下，青春期大鼠没有表现出显著的位置厌恶。成年德尔塔(9)-在醉酒状态下，THC处理的大鼠比青春期的大鼠产生更多的发声，这也表明更大的药物诱导的厌恶。经过10-15天的洗涤，成年和青少年Delta(9)-THC预处理的大鼠都表现出社会互动减少，而只有Delta(9)-THC预处理的青春期大鼠表现出显著的物体识别记忆障碍。在最后一次注射Delta(9)-THC 17天后，对大鼠进行安乐死，并用双向凝胶电泳法处理海马区组织。目前还没有证据表明血液中存在残留的Delta(9)-THC。蛋白质组学分析揭示了27个蛋白质，其中许多涉及调节氧化应激/线粒体功能和细胞结构，这些蛋白质在青少年Delta(9)-THC预处理的大鼠中与青少年对照组相比差异表达。在成人中，只有10个海马蛋白在Delta(9)-THC中与赋形剂处理的对照组相比有差异表达。总体而言，这些发现表明，与成年大鼠相比，青春期大鼠发现反复暴露Delta(9)-THC不那么令人厌恶，但与成年大鼠相比，大麻素暴露导致青春期大鼠更持久的记忆缺陷和海马区改变。
The current study examined whether adolescent rats are more vulnerable than adult rats to the lasting adverse effects of cannabinoid exposure on brain and behavior. Male Wistar rats were repeatedly exposed to Delta-9-tetrahydrocannabinol (Delta(9)-THC, 5 mg/kg i.p.) in a place-conditioning paradigm during either the adolescent (post-natal day 28+) or adult (post-natal day 60+) developmental stages. Adult rats avoided a Delta(9)-THC-paired environment after either four or eight pairings and this avoidance persisted for at least 16 days following the final Delta(9)-THC injection. In contrast, adolescent rats showed no significant place aversion. Adult Delta(9)-THC-treated rats produced more vocalizations than adolescent rats when handled during the intoxicated state, also suggesting greater drug-induced aversion. After a 10-15 day washout, both adult and adolescent Delta(9)-THC pretreated rats showed decreased social interaction, while only Delta(9)-THC pretreated adolescent rats showed significantly impaired object recognition memory. Seventeen days following their last Delta(9)-THC injection, rats were euthanased and hippocampal tissue processed using two-dimensional gel electrophoresis proteomics. There was no evidence of residual Delta(9)-THC being present in blood at this time. Proteomic analysis uncovered 27 proteins, many involved in regulating oxidative stress/mitochondrial functioning and cytoarchitecture, which were differentially expressed in adolescent Delta(9)-THC pretreated rats relative to adolescent controls. In adults, only 10 hippocampal proteins were differentially expressed in Delta(9)-THC compared to vehicle-pretreated controls. Overall these findings suggest that adolescent rats find repeated Delta(9)-THC exposure less aversive than adults, but that cannabinoid exposure causes greater lasting memory deficits and hippocampal alterations in adolescent than adult rats.