Departments of Anatomy & Neurobiology, University of California, Irvine, CA 92697, United States of America.
Departments of Anatomy & Neurobiology, University of California, Irvine, CA 92697, United States of America; Departments of Psychiatry & Human Behavior, University of California, Irvine, CA 92868, United States of America.
Neurobiol Dis. 2022 Jan;162:105565. doi: 10.1016/j.nbd.2021.105565. Epub 2021 Nov 25.
There is evidence that cannabis use during adolescence leads to memory and cognitive problems in young adulthood but little is known about effects of early life cannabis exposure on synaptic operations that are critical for encoding and organizing information. We report here that a 14-day course of daily Δ-tetrahydrocannabinol treatments administered to adolescent rats and mice (aTHC) leads to profound but selective deficits in synaptic plasticity in two axonal systems in female, and to lesser extent male, hippocampus as assessed in adulthood. Adolescent-THC exposure did not alter basic synaptic transmission (input/output curves) and had only modest effects on frequency facilitation. Nevertheless, aTHC severely impaired the endocannabinoid-dependent long-term potentiation in the lateral perforant path in females of both species, and in male mice; this was reliably associated with impaired acquisition of a component of episodic memory that depends on lateral perforant path function. Potentiation in the Schaffer-commissural (S-C) projection to field CA1 was disrupted by aTHC treatment in females only and this was associated with both a deficit in estrogen effects on S-C synaptic responses and impairments to CA1-dependent spatial (object location) memory. In all the results demonstrate sexually dimorphic and projection system-specific effects of aTHC exposure that could underlie discrete effects of early life cannabinoid usage on adult cognitive function. Moreover they suggest that some of the enduring, sexually dimorphic effects of cannabis use reflect changes in synaptic estrogen action.
有证据表明，青少年时期使用大麻会导致成年后出现记忆力和认知问题，但对于早期生活中接触大麻对编码和组织信息至关重要的突触活动的影响知之甚少。我们在这里报告，在青春期大鼠和小鼠中进行为期 14 天的每日 Δ-四氢大麻酚处理（aTHC）会导致雌性海马体中两个轴突系统的突触可塑性出现深刻但选择性的缺陷，在雄性中则程度较轻。青春期接触大麻不会改变基本的突触传递（输入/输出曲线），并且对频率易化只有适度的影响。然而，aTHC 严重损害了两种物种雌性和雄性小鼠外侧穿通路径中的内源性大麻素依赖性长时程增强作用；这与依赖外侧穿通路径功能的情节记忆成分的获得障碍可靠相关。在雌性中，aTHC 处理破坏了 Schaffer 联合（S-C）投射到 CA1 场的易化作用，而在雌性中仅观察到这种作用与雌激素对 S-C 突触反应的影响以及对 CA1 依赖性空间（物体位置）记忆的损害有关。所有结果均表明，aTHC 暴露具有性别二态和投射系统特异性的影响，这可能是早期生活中使用大麻对成年认知功能的离散影响的基础。此外，它们还表明，大麻使用的一些持久的、性别二态的影响反映了突触雌激素作用的变化。
