PSYCHOMOTOR STIMULANTS & AGGRESSION IN ANIMALS

精神运动兴奋剂

• 批准号: 3207465
• 负责人: KLAUS A MICZEK
• 金额: $ 23.08万
• 依托单位: TUFTS UNIVERSITY MEDFORD
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-09-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3207465
• 关键词: Saimiri; adrenergic receptor; aggression; analgesia; behavior test; central nervous system stimulants; cocaine; dextroamphetamine; dopamine receptor; drug abuse; drug addiction antagonist; drug tolerance; drug withdrawal; ethology; experience; hormones; laboratory mouse; laboratory rat; maternal behavior; neurochemistry; neuropeptide receptor; opiate alkaloid; prazosin; psychomotor function; psychopharmacology; receptor sensitivity; sex behavior; social behavior; social dominance; startle reaction

Stimulant abuse may engender explosive and seemingly unpredictable violent outbursts in certain individuals, whereas others withdraw entirely from social interactions. The specific aims of the proposed research are as follows: 1. How functionally specific or pervasive are the behavioral tolerance, sensitization and potentiation phenomena in the profile of opiate and psychomotor stimulant effects after distinctive experiences in situations of social conflict and affiliative behavior? 2. How do experience with certain social behaviors modulate the symptoms of opiate withdrawal? Which are the catecholaminergic mechanisms that mediate heightened aggressive and defensive reactions during opiate withdrawal? 3. How do experience with reproductive and aggressive behavior that are based on the hormonal status of the individual, particularly in females, influence the behavioral and physiological effects of opiates and psychomotor stimulants? 4. Are individual differences in sensitivity to amphetamine's and cocaine's acute and chronic behavioral effects linked to distinctive social experiences? We plan to conduct studies that will (1) parametrically determine the minimal and "optimal" social, aggressive, defensive and submissive behaviors that result in modulation of behavioral and physiological functions, (2) use biochemically identified selective ligands at different opiate receptor subtypes as well as dopaminergic and noradrenergic receptor subtypes as probes for functional assessments, and (3) quantitatively assess selected functions such as DA, DOPAC, NE, 5-HT, 5-HIAA in discrete fore- and midbrain regions, serum prolactin and corticosterone, telemetered heart rate, blood pressure, core temperature, pain and startle responses, motor activities, discriminative stimulus properties, maternal care behavior, sexual, social, aggressive, defensive, submissive and flight reactions. Additional experiments will investigate the effectiveness of acute morphine administration in comparison to incrementally longer morphine exposure to induce heightened aggressive behavior. Further experiments are designed to examine the receptor super- sensitivity proposal by challenging animals during opiate withdrawal with several selective dopaminergic and noradrenergic receptor agonists, first systemically, and subsequently by intra- cranial infusion into specific target regions. A final set of experiments will attempt to antagonize amphetamine and cocaine effects on social and aggressive behavior with prazosin and other drugs that interfere with noradrenergic and dopaminergic neurotransmission.

滥用兴奋剂可能会导致爆炸性的、看似 某些人会出现不可预测的暴力爆发，而 其他人则完全退出社交互动。 具体的 本研究的目的如下： 1. 功能如何 具体或普遍的是行为耐受性、敏感化 和阿片剂轮廓中的增强现象 独特经历后的精神运动兴奋作用 社会冲突和亲和行为的情况？ 2. 怎么做 某些社会行为的经历会调节症状 阿片戒断？ 儿茶酚胺能的有哪些 调节攻击性和防御性增强的机制 阿片戒断期间的反应？ 3. 体验如何 生殖和攻击行为是基于 个人的荷尔蒙状况，尤其是女性， 影响阿片类药物的行为和生理效应 精神运动兴奋剂？ 4.个体差异是否存在 对安非他明和可卡因的急性和慢性敏感性 行为效应与独特的社会经历有关？ 我们 计划进行研究，以（1）参数确定 最小和“最佳”的社交、攻击性、防御性和 导致行为和行为调节的顺从行为 生理功能，（2）利用生化鉴定选择性 不同阿片受体亚型的配体以及 多巴胺能和去甲肾上腺素能受体亚型作为探针 功能评估，以及（3）定量评估选定的 离散功能，如 DA、DOPAC、NE、5-HT、5-HIAA 前脑和中脑区域，血清催乳素和皮质酮， 遥测心率、血压、核心温度、疼痛 和惊吓反应、运动活动、辨别刺激 属性、产妇护理行为、性、社交、攻击性、 防御、顺从和逃跑反应。额外的实验 将研究急性吗啡的有效性 与逐渐延长吗啡的给药时间相比 暴露会诱发加剧的攻击行为。 更远 实验旨在检查受体超 通过在阿片类药物期间挑战动物来提出敏感性建议 用几种选择性多巴胺能和去甲肾上腺素能药物戒断 受体激动剂，首先全身给药，随后通过体内给药 向特定目标区域进行颅内灌注。 最后一组 实验将尝试拮抗安非他明和可卡因 哌唑嗪等对社交和攻击行为的影响 干扰去甲肾上腺素能和多巴胺能的药物 神经传递。