Renard Justine, Rosen Laura G, Loureiro Michael, De Oliveira Cleusa, Schmid Susanne, Rushlow Walter J, Laviolette Steven R
Addiction Research Group.
Department of Anatomy and Cell Biology.
Cereb Cortex. 2017 Feb 1;27(2):1297-1310. doi: 10.1093/cercor/bhv335.
Considerable evidence suggests that adolescent exposure to delta-9-tetrahydrocanabinol (THC), the psychoactive component in marijuana, increases the risk of developing schizophrenia-related symptoms in early adulthood. In the present study, we used a combination of behavioral and molecular analyses with in vivo neuronal electrophysiology to compare the long-term effects of adolescent versus adulthood THC exposure in rats. We report that adolescent, but not adult, THC exposure induces long-term neuropsychiatric-like phenotypes similar to those observed in clinical populations. Thus, adolescent THC exposure induced behavioral abnormalities resembling positive and negative schizophrenia-related endophenotypes and a state of neuronal hyperactivity in the mesocorticolimbic dopamine (DA) pathway. Furthermore, we observed profound alterations in several prefrontal cortical molecular pathways consistent with sub-cortical DAergic dysregulation. Our findings demonstrate a profound dissociation in relative risk profiles for adolescent versus adulthood exposure to THC in terms of neuronal, behavioral, and molecular markers resembling neuropsychiatric pathology.
大量证据表明，青少年接触大麻中的精神活性成分Δ9-四氢大麻酚（THC）会增加成年早期出现精神分裂症相关症状的风险。在本研究中，我们结合行为和分子分析以及体内神经元电生理学，比较青少年与成年大鼠接触THC的长期影响。我们报告称，青少年而非成年大鼠接触THC会诱导出类似于临床人群中观察到的长期神经精神样表型。因此，青少年接触THC会诱发行为异常，类似于精神分裂症相关的阳性和阴性内表型，以及中脑边缘多巴胺（DA）通路中的神经元过度活跃状态。此外，我们观察到几个前额叶皮质分子通路发生了深刻变化，这与皮质下多巴胺能失调一致。我们的研究结果表明，在类似于神经精神病理学的神经元、行为和分子标志物方面，青少年与成年大鼠接触THC的相对风险概况存在深刻差异。
