BENZODIAZEPINE OVERINDULGENCE AND DRUG INTERACTIONS

(1)苯二氮卓类药物口服强化疗效的启动 (BZs)将在动物中研究滥用摄入水平， 在时间表诱导的烦渴条件下的偏好程序。 一 可能降低口腔BZ的强化阈值， 精神兴奋剂，特别是咖啡因， BZ拮抗剂氟马西尼，以及血清药代动力学相关 对口服BZ的补益作用进行研究。 (2)的协同 咪达唑仑和咖啡因联合注射在干扰细- 运动任务的表现将使用各种自发的 和编程的运动测量。 这些研究可能暗示咖啡因 (and其他兴奋剂）在老年人的运动问题（特别是 下降），涉及BZ和不能还原为BZ镇静作用。 BZ-黄嘌呤协同作用的行为学和药理学共性 将被定性。 (3)增加的行为影响 在血清咖啡因的表观清除率中， 将探讨咪达唑仑暴露的可能性， BZ停药综合征可归因于咖啡因中毒。 （四） BZ-兴奋剂的急性和慢性药代动力学说明 组合将平行的行为研究，在划定的 BZ-黄嘌呤协同作用的机理。 (5)将有一项研究， 阿普唑仑-咖啡因相互作用可能的协同破坏 精细运动控制，这可能与触发或 恐慌症恶化 此外，BZ对茶碱的作用 将注意到行为效应与 治疗剂量的茶碱，特别是通过口服途径。

(1) The initiation of oral reinforcing efficacy for benzodiazepines (BZs) will be studied in animals at abusive intake levels using a drug preference procedure under schedule-induced polydipsia conditions. A possible decrease in the reinforcing threshold of oral BZs by psychomotor stimulants, particularly caffeine, a threshold shift by the BZ antagonist flumazenil, as well as the serum pharmacokinetics relevant to oral BZ reinforcing function, will be studied. (2) The synergistic action of combined midazolam and caffeine injections in disrupting fine- motor task performance will be analyzed using a variety of spontaneous and programmed motor measures. These studies may implicate caffeine (and other stimulants) in motor problems of the elderly (specifically falling) that involve BZs and are not reducible to BZ sedative action. The behavioral and pharmacologic generality of BZ-xanthine synergism will be characterized. (3) The behavioral implications of the increase in apparent clearance of serum caffeine that results from chronic exposure to midazolam will be explored with the possibility that part of the BZ discontinuance syndrome may be attributable to caffeinism. (4) Clarification of the acute and chronic pharmacokinetics of BZ-stimulant combinations will parallel behavioral studies in the delineation of the mechanism of BZ-xanthine synergism. (5) There will be study of a alprazolam-caffeine interactions for a possible synergistic disruption of fine-motor control, which might be relevant to triggering or worsening panic disorder. Also, the effect of BZs on theophylline's behavioral effects will be noted in relation to tremor produced by therapeutic doses of theophylline, particularly by the oral route.