Protective benefits of maternal behavior on susceptibility for drug abuse

母亲行为对药物滥用易感性的保护作用

• 批准号: 8116520
• 负责人: JILL B. BECKER
• 金额: $ 17.49万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8116520
• 关键词: 17 year old; Acute; Affect; Age; Amphetamines; Animals; Attenuated; Behavior; Birth; Caring; Cocaine; Cocaine Abuse; Cocaine Users; Corpus striatum structure; Data; Dopamine; Dose; Drug Addiction; Drug abuse; Drug usage; Exhibits; Female; Fostering; Fright; Gender; Goals; Human; Infant; Laboratories; Laboratory Animals; Lead; Learning; Maintenance; Maternal Behavior; Measures; Memory; Methods; Microdialysis; Microtus; Mothers; Motivation; Naltrexone; Nest Leaving; Neurobiology; Neurons; Nucleus Accumbens; Outcome; Pair Bond; Pathway interactions; Pharmaceutical Preparations; Pharmacological Treatment; Predisposition; Pregnancy; Rattus; Relapse; Reporting; Research; Risk; Self Administration; Self-Administered; Staging; Stress; Surveys; System; Testing; Weaning; Woman; age related; behavioral sensitization; cocaine exposure; cognitive function; drug of abuse; experience; improved; in vivo; male; men; motherhood; neurobehavioral; offspring; prairie vole; preference; protective effect; public health relevance; relating to nervous system; research study; response; social attachment

DESCRIPTION (provided by applicant): Drug abuse among young women is on the rise, with a recent report stating that 56 percent of cocaine users ages 12-17 are women. Women escalate more rapidly through all stages of drug addiction as compared to men, making them especially vulnerable to the deleterious effects of cocaine. Pharmacological treatments for cocaine abuse that are effective in men, such as naltrexone, are ineffective in females or even increase drug use. While it may be possible to develop gender-specific pharmacologic treatments for cocaine abuse in women, non-pharmacologic treatments are also needed. Research in laboratory animals and survey research with humans has indicated a potentially protective effect of the formation of strong social bonds with regards to drug abuse. The strongest social bond formed in rats is the mother-infant bond. Following the rearing of offspring, female rats demonstrate improved learning and memory, increased exploration and foraging ability, attenuated age-related decreases in cognitive function, and decreased neurobehavioral stress and fear responses, even after the offspring have been weaned. These beneficial alterations have been shown to persist for months after the offspring have left the nest, indicating relatively permanent neural reorganization. Importantly, these benefits of maternal behavior occur in nulliparous foster mothers and males that have been induced to act maternally, indicating that pregnancy and parturition are not required for these benefits to be seen. Both drugs of abuse and formation of social bonds induce changes in the neuronal targets of the mesolimbic dopamine pathway, in particular in the nucleus accumbens and striatum. When attachment to a conspecific or drug of abuse is induced, the ability of this neural system to form an attachment to alternate goals is reduced. So, male prairie voles that have pair-bonded with a female do not develop a conditioned place preference to a low dose of amphetamine, while non-bonded males do. Likewise, male voles that have exhibited sensitization to amphetamine do not readily form a pair-bond when presented with a female. Preliminary data from our laboratory have shown that primiparous females exhibit less behavioral sensitization with repeated cocaine administration than do nulliparous age-matched females. The experiments proposed here will test the hypothesis that beneficial effects of social bond formation during the maternal experience of caring for young (whether the female is parturient or not) can protect females from susceptibility for drug abuse. Specifically, experiments will examine if caring for young can affect cocaine self-administration behavior (i.e., the rate of acquisition, the motivation to self-administer cocaine, continuation of responding during periods of non-reinforcement, and persistence to take drug in the face of aversive outcomes), and/or the animals' endogenous response to repeated cocaine exposure using a behavioral sensitization paradigm and in vivo microdialysis. PUBLIC HEALTH RELEVANCE: The experiments proposed here will test the hypothesis that beneficial effects of social bond formation during the maternal experience of caring for young (whether the female is parturient or not) can protect females from susceptibility for drug abuse. Data generated from these experiments will provide a first step towards delineating neurobiological/neurobehavioral mechanisms that may attenuate drug taking in females and lead to identification of new methods to help treat women who are at risk for drug addiction.

描述（由申请人提供）：年轻女性滥用药物的情况正在上升，最近的一份报告指出，12-17岁的可卡因使用者中有56%是女性。与男子相比，妇女在吸毒成瘾的各个阶段升级得更快，使她们特别容易受到可卡因的有害影响。对男性有效的可卡因滥用药物治疗（例如纳曲酮）对女性无效，甚至会增加药物使用。虽然有可能开发针对女性可卡因滥用的性别特异性药物治疗，但也需要非药物治疗。对实验室动物的研究和对人类的调查研究表明，在药物滥用方面形成牢固的社会联系具有潜在的保护作用。在老鼠中形成的最强的社会纽带是母婴纽带。在养育后代后，雌性大鼠表现出改善的学习和记忆，增加的探索和觅食能力，减弱与年龄相关的认知功能下降，降低神经行为应激和恐惧反应，即使在后代断奶后。这些有益的改变已经被证明在后代离开巢穴后持续数月，表明相对永久的神经重组。重要的是，这些母亲行为的好处发生在未经生育的养母和男性已被诱导采取母性行为，这表明怀孕和分娩是不需要这些好处被看到。滥用药物和社会联系的形成都会诱导中脑边缘多巴胺通路的神经元靶点发生变化，特别是在中脑边缘核和纹状体。当对同种或滥用药物的依恋被诱导时，这种神经系统形成对替代目标的依恋的能力就会降低。因此，与雌性配对的雄性草原田鼠不会对低剂量的安非他明产生条件性位置偏好，而非配对的雄性则会。同样，对安非他明有敏感性的雄性田鼠在与雌性田鼠接触时也不容易形成配对。我们实验室的初步数据表明，与年龄匹配的未经产女性相比，经产女性在重复可卡因给药时表现出较少的行为致敏性。这里提出的实验将测试的假设，社会纽带的形成过程中的母亲照顾年轻的经验（无论女性是否是产妇）的有益影响，可以保护女性从药物滥用的易感性。具体来说，实验将检查照顾年轻人是否会影响可卡因自我给药行为（即，获得的速率、自我施用可卡因的动机、在非强化期间响应的持续性、以及在面对令人厌恶的结果时坚持服药），和/或使用行为敏化范例和体内微透析的动物对重复可卡因暴露的内源性响应。 公共卫生关系：这里提出的实验将测试的假设，社会纽带的形成过程中的母亲照顾年轻的经验（无论女性是否是产妇）的有益影响，可以保护女性从药物滥用的易感性。从这些实验中产生的数据将提供第一步描绘神经生物学/神经行为机制，可能会减少女性吸毒，并导致识别新的方法，以帮助治疗妇女谁是在吸毒成瘾的风险。