Neurodevelopmental Effects of Adolescent Cannabis Use

青少年使用大麻对神经发育的影响

• 批准号: 7162434
• 负责人: YASMIN L. HURD
• 金额: $ 8.1万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7162434
• 关键词: age difference; behavioral /social science research tag; cannabinoid receptor; cannabinoids; central neural pathway /tract; cerebral cortex; developmental neurobiology; disease /disorder proneness /risk; dopamine; drug abuse; heroin; immature animal; laboratory rat; limbic system; marijuana abuse; psychopharmacology; receptor binding; reinforcer; self medication; substance abuse related behavior

DESCRIPTION (provided by applicant): Marijuana (cannabis sativa) use during adolescence normally predates the use of "heavy" drugs such as heroin in later life, which has raised speculations as to possible "gateway" effects of marijuana. Factors such as drug-associated environment and inherent individual differences (e.g., impulsivity, hyperactivity), which predates early drug use and can influence neurodevelopment during adolescence, appear to increase the risk for substance abuse disorders. The mesocorticolimbic system (MCLS) is critically involved in, e.g., emotional regulation, reward, and motivation and express significant levels of cannabinoid receptors (CB1). We have observed that cannabis-exposed human fetuses have impaired dopamine (DA)-related gene expression in the amygdala, a component of the MCLS (which also includes the nucleus accumbens (NAcc), ventral tegmental area (VTA), and medial prefrontal cortex (mPFC)). Moreover, we found that adolescent rats administered THC (the psychoactive component of cannabis) have increased heroin intake in adulthood suggesting a link between the cannabinoid and opioid systems. It is the goal of this proposal to identify neurobiological alterations in MCLS structures that can account for the effects of THC exposure during adolescence on heroin self-administration in adulthood. In vivo DA levels as well as gene expression and receptor binding linked to the CB1, opioid neuropeptides, and DA neural systems will be studied in MCLS structures in adult rats exposed to THC during adolescence. The impact of risk factors such as behavioral individual differences (e.g., high behavioral activity, high impulsivity) and the environmental context of THC exposure will also be evaluated in regard to their influence on heroin self-administration behavior and neurobiology. These studies should provide information as to whether there exist a long-term impact of THC exposure during development to substantiate a neurobiological "gateway" hypothesis and, if so, help to identify potential risk factors in adolescents that can influence the risk for heroin abuse in adulthood.

描述（由申请人提供）： 大麻（大麻sativa）在青春期的使用通常早于使用“重型”药物（例如海洛因）在后来的生命中，这引起了人们对大麻的可能“网关”影响的猜测。诸如药物相关的环境和固有的个体差异（例如，冲动性，多动症）诸如早期药物使用并可能影响青春期神经发育的因素似乎增加了药物滥用障碍的风险。中皮质降临系统（MCLS）至关重要的是，例如情绪调节，奖励和动机，并表达大麻素受体的显着水平（CB1）。 我们已经观察到，大麻暴露的人类胎儿在杏仁核（MCLS的一个成分（还包括伏隔核）（NACC），腹侧段段区域（VTA）和内侧前纹状体前叶状细胞（MPFC）中，杏仁核的多巴胺（DA）相关基因表达受损（DA）相关基因表达。此外，我们发现施用THC的青少年大鼠（大麻的精神活性成分）在成年期间增加了海洛因摄入量，这表明大麻素和阿片类药物系统之间存在联系。该提案的目的是确定MCLS结构中的神经生物学改变，这些变化可以解释青春期在青春期对海洛因自我管理的影响。体内DA水平以及与CB1，阿片类神经肽和DA神经系统相关的基因表达和受体结合，将在青春期暴露于THC的成年大鼠的MCLS结构中研究。诸如行为个体差异（例如，高行为活动，高冲动性）和THC暴露环境环境等风险因素的影响也将在其对海洛因自我给药行为和神经生物学的影响方面进行评估。这些研究应提供有关开发过程中THC暴露是否长期影响的信息，以证实神经生物学的“网关”假设，如果是的，则有助于确定可能影响成年后海洛因滥用风险的潜在危险因素。