Developmental Pharmacology of Cannabinoids

大麻素的发育药理学

• 批准号: 6770849
• 负责人: JENNY L. WILEY
• 金额: $ 26.25万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-10 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6770849
• 关键词: age difference; animal developmental psychology; autoradiography; behavior test; behavioral /social science research tag; cannabinoid receptor; cannabinoids; catalepsy; chordate locomotion; developmental neurobiology; disease /disorder model; dopamine agonists; growth /development; hypothermia; laboratory rat; marijuana abuse; neuropharmacology; newborn animals; pain; pharmacokinetics; receptor expression

DESCRIPTION (provided by applicant): Adolescence represents a developmental time point during which substance abuse often begins. Although the most prevalently used illicit drug during adolescence is marijuana, little is known about short- or long-term effects of its use during development. The major hypotheses of this proposal are that (1) developing animals will be more sensitive to the effects of delta9-tetrahydrocannabinol (delta9-THC), the primary psychoactive constituent of marijuana, than are adult animals and (2) chronic dosing with delta9-THC during development will produce long-term changes in response to challenges with cannabinoids in later life such that animals are less sensitive to the effects of cannabinoids. In order to test the first hypothesis, rats of different ages (postnatal day 22 to adult) will be administered acute doses of delta9-THC; subsequently, they will be evaluated in vivo procedures designed to measure cannabinoid activity (locomotion, body temperature, antinociception, and catalepsy). In addition, we will investigate the role of metabolism in any observed age differences in pharmacological effects. In order to test the second hypothesis, rats will be chronically injected with delta9-THC during development. After reaching adulthood, these animals will be evaluated in behavioral procedures to evaluate cannabinoid sensitivity, cognition, timing ability, and the reinforcing efficacy of food. In addition to baseline activity in these procedures, the effects of challenges with delta9-THC and other cannabinoids will also be assessed in the rats. In order to determine possible underlying changes in cannabinoid (CB1) receptor binding and distribution, autoradiography of the brains of rats that received identical chronic injection regimens will be performed using [3H]SR141716A as a radioligand. In addition, functioning of these receptors will be measured through use of [35S]GTPgammaS binding. The proposed studies will provide empirical information on acute and long-term effects of delta9-THC on the developing brain and behavior. This information may also help to provide a more rational basis for making treatment decisions concerning adolescents who abuse marijuana.

描述（由申请人提供）：青春期代表了经常开始滥用药物的发育时间点。尽管青春期最普遍使用的非法药物是大麻，但对其在发育过程中使用的短期或长期影响知之甚少。 The major hypotheses of this proposal are that (1) developing animals will be more sensitive to the effects of delta9-tetrahydrocannabinol (delta9-THC), the primary psychoactive constituent of marijuana, than are adult animals and (2) chronic dosing with delta9-THC during development will produce long-term changes in response to challenges with cannabinoids in later life such that animals are less sensitive to the effects of大麻素。为了检验第一个假设，将服用不同年龄的大鼠（成年后第22天）的大鼠。随后，将在旨在测量大麻素活性（运动，体温，抗伤害感受和催化症）的体内程序中评估它们。此外，我们将研究代谢在任何观察到的年龄差异在药理作用中的作用。为了检验第二个假设，在发育过程中将长期向Delta9-THC注射大鼠。成年后，将在行为程序中评估这些动物，以评估大麻素的敏感性，认知，时机能力以及食物的增强功效。除了这些程序中的基线活性外，在大鼠中还将评估Delta9-THC和其他大麻素的挑战的影响。为了确定大麻素（CB1）受体结合和分布的潜在变化，将使用[3H] SR141716A作为放射性物体进行接受相同慢性注射方案的大鼠大脑的放射自显影。另外，这些受体的功能将通过使用[35S] GTPGAMMAS结合来测量。拟议的研究将提供有关Delta9-THC急性和长期影响对发育中的大脑和行为的急性和长期影响的经验信息。这些信息还可能有助于提供更合理的基础，以制定有关滥用大麻的青少年的治疗决策。