Drugs as conditioned reinforcers and/or enhancers of social reward in adolescents

描述（由申请人提供）：大多数吸毒者在青春期开始吸毒，通常是在他们的同伴鼓励和加强他们行为的社会环境中，然而很少有临床前研究调查社会奖励如何影响药物滥用和依赖的开始和维持。本研究的目的是为此目的建立一个动物模型。本文将探讨两种可能影响青少年吸毒和寻求毒品行为的社会奖励互动假说：1)药物的药理作用可能协同增强社会互动的奖励效应；2)药物可能通过与社会互动配对获得条件强化效应。该提案的重点是尼古丁和社会奖励之间的相互作用。尼古丁是烟草制品中的一种药理学物质，它主要负责强化和产生吸烟的依赖效应，而与其他吸烟者交往的愿望有助于青少年开始吸烟。此外，啮齿类动物的自我给药研究发现，尼古丁不仅能增强，而且还能增强其他刺激的增强作用，比如与尼古丁传递一起出现的反应偶然线索。对其他药物的研究表明，药物状态本身没有强化作用，但可以通过与自然奖励相结合来获得条件强化效应。因此，我们推断，在早期使用期间，尼古丁状态可能通过与社会强化相关联而获得条件强化效应，这样，这些效应加上其自身的轻度强化效应，使尼古丁具有高度强化作用。社会奖励将使用我们最近开发的条件位置偏好方法来衡量。提出的研究的第一个目的是建立一个条件位置偏好（CPP）方法来评估静脉注射尼古丁的奖励效果。接下来，我们将研究尼古丁增强社会奖励- cpp的能力。最后，实验将检验先前的尼古丁与社会互动的配对是否会促进尼古丁的习得，并在维持期间增加尼古丁的摄入量。据我们所知，这些实验将是第一次研究社会互动对动物尼古丁自我给药的影响。动物模型将允许研究涉及药物：社会奖励相互作用的神经机制，因此，可能为涉及社会相互作用的成瘾和预防/干预策略的发展提供新的见解。药物滥用和依赖是主要的健康和社会问题。拟议的研究将调查关于尼古丁的奖励效应和可能导致这些疾病的社会互动之间相互作用的新假设。这一发现可能会引发对参与这些相互作用的神经机制的一系列调查，进而为理解和治疗药物滥用和依赖提供见解。

DESCRIPTION (provided by applicant): Most drug addicts begin taking drugs during adolescence, often in social settings in which their peers encourage and reinforce their behavior, yet little preclinical research has investigated how social reward influences initiation and maintenance of drug abuse and dependence. The objective of the proposed research is to develop an animal model for this purpose. Two hypotheses regarding drug: social reward interactions that may contribute to drug-taking and drug-seeking behaviors in adolescents will be examined: 1) pharmacologic effects of drugs may synergistically enhance the rewarding effects of social interaction, and 2) drugs may acquire conditioned reinforcing effects via pairing with social interaction. The proposal focuses on interactions between nicotine and social reward. Nicotine is the pharmacologic agent in tobacco products that is primarily responsible for the reinforcing and dependence-producing effects of smoking and desire to affiliate with other smokers contributes to initiation of smoking in adolescents. Furthermore, rodent self-administration studies have found that not only is nicotine reinforcing, but it is also capable of enhancing the reinforcing effects of other stimuli, such as response-contingent cues that appear in conjunction with nicotine delivery. Research with other drugs suggests that drug states that are not reinforcing on their own can acquire conditioned reinforcing effects via pairing with natural rewards. Therefore, we reasoned that during early use, the nicotine state may acquire conditioned reinforcing effects through association with social reinforcement, such that these effects add to its own mildly reinforcing effects rendering nicotine highly reinforcing. Social reward will be measured using a conditioned place preference method we have recently developed. The first aim of the proposed research is to establish a conditioned place preference (CPP) method for assessing rewarding effects of intravenous nicotine administration. Next, the ability of nicotine to enhance social reward-CPP will be investigated. Finally, experiments will examine whether previous pairings of nicotine with social interaction will facilitate acquisition, and enhance intake during maintenance, of nicotine self-administration. To our knowledge, these experiments will be the first to examine the influence of social interaction on nicotine self-administration in animals. The animal model will allow investigation of neural mechanisms involved in drug: social reward interactions, and therefore, may offer novel insight into the development of addiction and prevention/intervention strategies involving social interaction. Drug abuse and dependence are major health and societal problems. The proposed research will investigate novel hypotheses regarding the interaction between the rewarding effects of nicotine and social interaction that may contribute to these disorders. The findings could potentially initiate a line of investigation on neural mechanisms involved in these interactions, which may in turn provide insight for understanding and treating drug abuse and dependence.