GLUTAMATE AND THE SELF ADMINISTRATION OF AMPHETAMINES

描述：（改编自申请人摘要） 本申请中提出的实验是一个持续的实验的一部分。 申请人旨在确定神经基础的研究工作 药物诱导的行为敏感化， 及其表达的意义。精神兴奋剂，如 安非他明和鸦片类药物，两者都是自我- 由人类和实验室动物管理，产生运动 activation.反复接触这些药物会产生长期的 增强了它们引发运动的能力， 几周到几个月后再次接触药物， 比最初看到的行为激活。更重要的是，Prior 暴露于安非他明注射的这种致敏方案也 能长期增强动物的易感性 然后自己给药。 相当多的证据将中脑多巴胺神经元与 精神运动产生的运动和支持的自我管理 兴奋剂在这个神经元系统中的敏化作用也与 高于运动的长期增强，似乎与 增强了动物自我给药的倾向。 其他研究结果表明兴奋性氨基酸的重要贡献 酸性谷氨酸对运动神经元的诱导和表达 安非他明致敏然而，人们对它知之甚少。 这种神经递质对药物服用的促进作用 通过暴露于致敏药物方案而产生。通过研究 安非他明自我管理的大鼠，拟议的实验将 我试图通过回答三个问题来阐明这一贡献 问题： 问题1：归纳。已知的阻断诱导的方法 对安非他明的自发致敏，如致敏前 具有离子型和代谢型特异性拮抗剂的注射剂 谷氨酸受体，也阻止了自我管理的便利化 的药物？ 问题2：表达。先前接触安非他明是否会增强 中脑终末区细胞外谷氨酸水平 多巴胺神经元在随后的自我管理的药物 以及在这种行为消失后恢复这种行为？ 问题3：表达。先前接触安非他明是否会增强 谷氨酸受体亚型选择性配体在该位点的能力， 随后影响药物的自我给药以及 灭绝后的恢复？

DESCRIPTION: (Adapted From The Applicant's Abstract) The experiments proposed in this application are part of a continuing research effort by the applicant aimed at determining the neural basis of drug-induced behavioral sensitization and at understanding the nature and significance of its expression. Psychomotor stimulants like the amphetamines as well as opiate drugs, both of which are self- administered by man and laboratory animals, produce locomotor activation. Repeated exposure to these drugs produces long-term enhancements in their ability to elicit locomotion so that subsequent re-exposure to the drug, weeks to months later, produces greater behavioral activation than seen initially. More importantly, prior exposure to such sensitizing regimens of amphetamine injections is also known to produce long lasting enhancements in animals' predisposition to subsequently self-administer the drug. Considerable evidence links mesoaccumbens dopamine neurons to the locomotion produced and the self-administration supported by psychomotor stimulants. Sensitization in this neuronal system also parallels the above long-term enhancements in locomotion and appears to be associated with enhancements in animals' predisposition to self-administer drug. Other findings indicate important contributions by the excitatory amino acid glutamate both to the INDUCTION and EXPRESSION of locomotor sensitization by amphetamines. Little is known, however, of the contribution of this neurotransmitter to the facilitation of drug taking produced by exposure to sensitizing drug regimens. By studying amphetamine self-administration in rats, the proposed experiments will attempt to elucidate this contribution by seeking to answer three questions: QUESTION 1: INDUCTION. Do manipulations known to block the induction of locomotor sensitization to amphetamine, such as preceding sensitizing injections with antagonists specific for ionotropic and metabotropic glutamate receptors, also block the facilitation of self-administration of the drug? QUESTION 2: EXPRESSION. Does prior exposure to amphetamine enhance extracellular levels of glutamate in the terminal field of mesoaccumbens dopamine neurons during the subsequent self-administration of the drug and reinstatement of this behavior after it has been extinguished? QUESTION 3: EXPRESSION. Does prior exposure to amphetamine enhance the ability of glutamate receptor subtype selective ligands in this site to subsequently influence the self-administration of the drug as well as its reinstatement after extinction?