Social buffering and vulnerability to nicotine reward

社会缓冲和对尼古丁奖励的脆弱性

• 批准号: 8459819
• 负责人: Natalie Ann Cole-Peartree
• 金额: $ 4.22万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-11 至 2015-01-10
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8459819
• 关键词: Acute; Address; Adolescence; Adolescent; Adrenal Cortex Hormones; Amygdaloid structure; Animal Experimentation; Animal Model; Animals; Anterior; Anxiety; Area; Attention; Attenuated; Aversive Stimulus; Beds; Behavior; Behavioral; Behavioral Mechanisms; Biological; Birds; Brain; Brain region; Buffers; Cell Nucleus; Cells; Cessation of life; Corticosterone; Country; Coupled; Dependence; Development; Distress; Dose; Drug Addiction; Drug Exposure; Drug abuse; Emotional; Exhibits; Gene Proteins; Health; Human; Immediate-Early Genes; Immunohistochemistry; Injection of therapeutic agent; Intervention; Label; Laboratories; Literature; Male Adolescents; Measures; Mediating; Modeling; Neurons; Nicotine; Nicotine Dependence; Nucleus Accumbens; Output; Pathway interactions; Pharmaceutical Preparations; Physiological; Pre-Clinical Model; Prevention strategy; Process; Psychological reinforcement; Rattus; Recovery; Relative (related person); Research; Resources; Rewards; Rodent; Sheep; Smoking; Social Environment; Social Interaction; Social Reinforcement; Social isolation; Staging; Stimulus; Stress; Structure; Structure of terminal stria nuclei of preoptic region; System; Testing; Time; Tissues; Translating; United States; addiction; biological adaptation to stress; dependence relapse; drug of abuse; drug reward; emotional stimulus; excitatory neuron; experience; hypothalamic-pituitary-adrenal axis; inhibitory neuron; motivated behavior; neuromechanism; nonhuman primate; peer; pre-clinical; preference; public health relevance; relating to nervous system; response; reward processing; social; stressor; young adult

DESCRIPTION (provided by applicant): There is a significant need for better prevention and intervention strategies for smoking and nicotine dependence. Progress in this area relies upon understanding the biological and behavioral mechanisms involved in various stages of addiction, including initiation. Initial drug experiences typically take place in adolescence and nearly always in the presence of peers who provide social reinforcement for the behavior, yet the neural mechanisms involved in social influences on drug initiation are poorly understood. Animal models demonstrate that in adolescents, social interactions enhance the rewarding effects of commonly abused drugs, including nicotine. Nicotine and other drugs of abuse elevate corticosteroids (CORT) via activation of the hypothalamic-pituitary-adrenal (HPA) axis, which is the body's response to stressors. Social buffering is a well- known phenomenon in the stress literature in which the presence of a conspecific promotes better recovery from stressful stimuli by alleviating negative physiological and behavioral responses to stress. Stress and reward both activate mesocorticolimbic pathways in the brain, which are involved in processing emotional stimuli and translating it into motivated behavior. These pathways and the HPA axis are reciprocally regulated. Recently, our lab has found that nicotine-induced CORT elevation is attenuated by a social context. Therefore, we hypothesize that social buffering during initial the experience with nicotine renders adolescents more resilient to initial anxiogenic effects of the drug by inhibiting the HPA axis and modulating mesocorticolimbic processing, resulting in increased reward salience. To test our hypothesis, we will investigate nicotine-induced HPA-axis activation and anxiety-related behavior in an open field in rats tested alone versus in familiar pairs. We will then examine whether this initial drug experience renders the next drug experience more rewarding in rats that were with another rat following their first injection relatie to those that were alone using the conditioned place preference (CPP) model. Finally, we will measure activation of brain regions implicated in processing stressful stimuli using expression of the immediate early gene protein product, Fos as a marker. Examination of neural activation will be focused primarily on identifying excitatory and inhibitory cells within the bed nucleus of stria terminals (BNST), a region of the brain highly implicated in anxiety processing. We predict that rats that receive social interaction in combination with nicotine will demonstrate less anxiety-lik behaviors in the open field test, show an attenuated CORT response, display enhanced drug-CPP, and exhibit less activation of stress and anxiety-related brain structures. The findings will aid in elucidating the mechanisms involved in social and nicotine reward interactions during initial drug exposure. This information is significant and may inform the development of new prevention and intervention strategies for drug abuse because the degree to which one finds the first drug experience rewarding is thought to predict the propensity for drug abuse and dependence.

描述（由申请人提供）：对于吸烟和尼古丁依赖的更好的预防和干预策略存在显著需求。这一领域的进展依赖于对成瘾各个阶段（包括初始阶段）所涉及的生物学和行为机制的理解。最初的药物体验通常发生在青春期，几乎总是在同龄人的存在下，他们为行为提供社会强化，但对药物启动的社会影响所涉及的神经机制知之甚少。动物模型表明，在青少年中，社会互动增强了包括尼古丁在内的常见滥用药物的奖励效应。尼古丁和其他滥用药物通过激活下丘脑-垂体-肾上腺（HPA）轴来提高皮质类固醇（CORT），HPA轴是身体对压力的反应。社会缓冲是压力文献中众所周知的现象，其中同种的存在通过减轻对压力的负面生理和行为反应来促进从压力刺激中更好地恢复。压力和奖励都会激活大脑中的中皮质边缘通路，该通路参与处理情感刺激并将其转化为有动力的行为。这些途径和HPA轴是受神经调节的。最近，我们的实验室发现，尼古丁诱导的CORT升高被社会背景减弱。因此，我们假设，在最初接触尼古丁的过程中，社交缓冲通过抑制HPA轴和调节中皮质边缘加工，使青少年对药物最初的焦虑作用更具弹性，从而增加奖励显着性。为了验证我们的假设，我们将研究尼古丁诱导的HPA轴激活和焦虑相关的行为在一个开放的领域在大鼠单独测试与熟悉的对。然后我们将使用条件性位置偏爱（CPP）模型，研究这种最初的药物体验是否会使第一次注射后与另一只大鼠在一起的大鼠的下一次药物体验更有意义。最后，我们将测量激活的大脑区域参与处理应激刺激使用表达的立即早期基因蛋白质产物，Fos作为标记。神经激活的检查将主要集中在识别纹状体床核内的兴奋和抑制细胞 神经末梢（BNST）是大脑中高度参与焦虑处理的区域。我们预测，接受社会互动与尼古丁结合的大鼠在旷场试验中表现出较少的焦虑样行为，表现出减弱的CORT反应，表现出增强的药物CPP，并表现出较少的应激和焦虑相关的大脑结构激活。这些发现将有助于阐明在最初的药物暴露期间参与社会和尼古丁奖励相互作用的机制。这一信息意义重大，可以为制定新的药物滥用预防和干预战略提供信息，因为人们认为，首次吸毒的奖励程度可以预测药物滥用和依赖的倾向。