Investigating the dose-response of prenatal-THC exposure in adolescent mice

MRC：Jessica Myatt：MC_ST_BNDU_2019在世界各地，关于娱乐性使用大麻合法化的规则正在发生变化。这导致人们认为大麻用途：使用是安全的：因此，人们仍然没有意识到可能产生的健康风险。通常在大麻产品中发现的δ-9-四氢大麻酚（THC）的浓度正在上升-这是一个令人担忧的问题，因为THC已知具有精神活性。这是令人担忧的，因为它可能意味着一个人可能会在运动功能，行为，感知或思维方面表现出严重的干扰，或者例如幻觉。以前的研究现在已经过时，因为它们是在THC浓度仍然很低的时候进行的-在过去的20年中，THC浓度从大约1.5-4%上升到29%。此外，研究表明，母亲和父亲在怀孕期间使用大麻会增加后代患精神病的风险。此外，大麻/大麻产品正在被用来抵消怀孕期间的恶心，因此，必须尽早进行研究，以解决THC暴露可能对后代产生的影响。人们普遍认为，精神分裂症等疾病具有实质性的神经发育基础。这意味着环境和遗传风险因素的证据可能导致大脑发育中断或改变后的广泛结果。总的来说，THC浓度的增加，以及这种疾病的实质性神经发育基础，因此可能导致人群中出现精神障碍的风险。为了开始解决这个问题，本项目将调查出生前暴露于THC对啮齿动物青少年后代神经发育的剂量依赖性影响。后代将在出生前接触两种不同浓度的THC或对照物质之一。在幼崽出生并进入青春期后，他们将被扫描以获取大脑的图像，间隔一周，这将使我们能够寻找任何结构变化。还将使用行为任务对后代进行评估，以确定其相关行为是否有任何变化。收集的科学数据可以提供知识，以指导旨在预防未来可能与出生前接触THC有关的公共卫生挑战的政策。

MRC : Jessica Myatt : MC_ST_BNDU_2019Across the world, rules regarding the legalisation of the recreational use of cannabis are changing. This is leading to a perception that cannabis is safe to use: people, therefore, remain unaware of possible consequential health risks. The concentration of delta-9-tetrahydrocannabinol (THC), often found in cannabis products, is rising - a concern as THC is known to have psychoactive effects. This is concerning as it could mean a person may display significant disturbances in motor function, behaviour, perception or thinking, or hallucinate for example. Previous studies are now outdated as they were undertaken when the concentration of THC remained low - in the last 20 years THC concentration has risen from around 1.5-4% up to 29%. Furthermore, it has been shown that maternal and paternal cannabis use during pregnancy increases the risk of psychotic-like experiences in offspring. Additionally, cannabis/cannabis products are being used to counteract nausea in pregnancy, therefore it is imperative that studies addressing the effect THC exposure may have on offspring are carried out sooner rather than later. There is general acceptance for disorders such as schizophrenia, to have a substantial neurodevelopmental basis. This means evidence for both environmental and inherited risk factors that could result in a wide range of outcomes following disrupted or altered development of the brain. Taken together, the increase in the concentration of THC, alongside the substantial neurodevelopmental basis of such disorders, could, therefore, result in an emergent risk of psychotic disorders within the population. To begin to address this, this project will investigate the dose-dependent effects of exposure to THC before birth on the neurodevelopment of adolescent offspring in rodents. Offspring will be exposed to one of two different concentrations of THC or a control substance before birth. After pups have been born and reached adolescence, they will be scanned to acquire images of the brain a week apart which will allow us to look for any structural changes across time. The offspring will also be assessed using behavioural tasks to determine if there are any changes in their associated behaviour. Scientific data collected may provide knowledge to guide policies aimed to prevent future public health challenges that could be associated with exposure to THC before birth.