COCAINE, CAFFEINE AND NICOTINE--ORAL ABUSE AND BEHAVIOR

描述：（申请人摘要） 大鼠实验将确定药物剂量（可卡因，PCP， 咖啡因、咪达唑仑、己巴比妥、尼古丁）， 胃内或IV插管，取决于饮用特定流体， 建立一个口服偏好的解决方案，无论是（a）一个 药物溶液或（B）中性风味溶液，以确定 口服药物偏好和滥用是否可以仅仅由 药理学事件，尚未明确建立相关性。 的 药理学事件（例如，血清药物和代谢物水平） 胃和静脉药物输送将被划定，以及 胃内和IV药物强化阈值，以影响 药物强化的药代动力学-药效学建模， 这种澄清在设计药物激动剂疗法中可能是有用的。 的 开始和持续口服药物的药理学事件 自我管理将被比作环境事件 （时间表诱导的烦渴），也可引起慢性口服药物 自我管理。 药物自我给药的程度 妥协，随后的时间行为将衡量行为毒性 急性和慢性吸毒的后果。 时间刺激控制 影响口服可卡因溶液复吸的药理学因素 优先将被评估。

DESCRIPTION: (Applicant's Abstract) Experiments with rats will determine whether drug doses (cocaine, PCP, caffeine, midazolam, hexobarbital, nicotine) that are delivered by either intragastric or IV cannula contingent upon drinking a specific fluid can institute an oral preference for the solution drunk, whether it is (a) a drug solution or (b) a neutral-flavored solution, in order to ascertain whether oral drug preferences and abuse can be initiated solely by pharmacological events, a relation not yet clearly established. The pharmacological events (e.g., serum drug and metabolite levels) consequent to gastric and IV drug delivery will be delineated, as well as the intragastric and IV drug reinforcement thresholds, to effect the pharmacokinetic-pharmacodynamic modeling of drug reinforcement, which clarification may prove useful in the design of drug agonist therapies. The pharmacological events initiating and sustaining oral drug self-administration will be compared to the environmental events (schedule-induced polydipsia) which also can give rise to chronic oral drug self-administration. The degree to which drug self-administration compromises ensuing timing behavior will measure the behaviorally toxic consequences of acute and chronic drug-taking. Temporal, stimulus control, and pharmacological factors affecting the relapse to oral cocaine solution preference will be evaluated.