Sex differences in the escalation of oral phencyclidine (PCP) self-administration under FR and PR schedules in rhesus monkeys
Sex differences in the escalation of oral phencyclidine (PCP) self-administration under FR and PR schedules in rhesus monkeys
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DOI：
10.1007/s00213-005-2182-x
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发表时间：
2005-07-01
影响因子：
3.4
通讯作者：
Morgan, AD
中科院分区：
文献类型：
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作者：
Carroll, ME;Batulis, DK;Morgan, AD
基本原理：对雄性大鼠的研究表明，长期接触（LgA）与短期接触（ShA）静脉注射可卡因和海洛因自我给药导致药物摄入量增加，随后剂量反应函数上移。本实验的目的是将这些结果扩展到雄性和雌性恒河猴以及在固定比例（FR）和渐进比例（PR）下口服苯环己哌啶（PCP）的自我给药schedules.Methods:成年恒河猴（7只雌性和9只雄性）在每日ShA 3小时期间，按照FR 16和FR 16的同步时间表口服自我给药五氯苯酚（0.25毫克/毫升）和水。由于雌性动物的体重低于雄性动物，因此每次液体给药（0.6 ml）表示雌性动物的单位剂量mg/ kg高于雄性动物，但药物浓度mg/ ml保持恒定。然后使用并行PR PR方案获得浓度-反应函数（0.125、0.25、0.5和1.0 mg/ ml）。接下来，五氯苯酚和水在LgA 6小时会议期间根据同时FR 16 FR 16时间表提供21天。然后重新测试的猴子下，同时FR 16 FR 16和PR PR条件下，在ShA sessions.Results：根据最初的ShA同时FR 16 FR 16时间表，女性和男性没有不同的PCP交付或摄入量（毫克/公斤），但是，在LGA，男性和女性有更多的PCP交付相比，ShA。在LgA期间，男性的五氯苯酚分娩量超过女性，但女性的五氯苯酚摄入量（毫克/千克）高于男性。此外，在为期21天的LgA期的前3天至后3天，雄性和雌性的五氯苯酚（而非水）输送量和五氯苯酚毫克/千克摄入量均显著增加。随后的ShA FR 16 FR 16性能没有性别差异，但在两种性别中均显著高于第一个ShA期。在第二个ShA期间（与第一个ShA期间相比），浓度-PR时间表和PCP摄入量（mg/ kg）显着上升，雌性的mg/ kg摄入量显着超过雄性。结论：雄性和雌性恒河猴在LgA至PCP期间以及LgA后发生的ShA期间（与之前相比）均表现出PCP自我给药的升级。在PR时间表下，两者均显示浓度x摄入量（mg/ kg）函数垂直向上移动，并且雌性在该测量上超过雄性。PCP和猴子的这些研究结果与先前在雄性大鼠中进行的递增研究中可卡因剂量反应函数的垂直向上移动以及药物滥用其他几个阶段中性别差异（F > M）的报告一致。
Rationale: Studies with male rats indicate that long access (LgA) vs short access (ShA) to i.v. cocaine and heroin self-administration leads to an escalation of drug intake and a subsequent upward shift of the dose-response function.Objective: The purpose of this experiment was to extend these results to male and female rhesus monkeys and oral phencyclidine (PCP) self-administration under fixed-ratio (FR) and progressive-ratio ( PR) schedules.Methods: Adult rhesus monkeys ( seven females and nine males) orally self-administered PCP (0.25 mg/ml) and water under concurrent FR 16 FR 16 schedules during daily ShA 3-h sessions. Since females weighed less than males, each liquid delivery (0.6 ml) represented a higher unit dose mg/ kg for females than males, but drug concentration mg/ ml remained constant. Concurrent PR PR schedules were then used to obtain a concentration-response function (0.125, 0.25, 0.5, and 1.0 mg/ ml). Next, PCP and water were available during LgA 6-h sessions under concurrent FR 16 FR 16 schedules for 21 days. The monkeys were then retested under the concurrent FR 16 FR 16 and PR PR conditions during ShA sessions.Results: Under the initial ShA concurrent FR 16 FR 16 schedules, females and males did not differ on PCP deliveries or intake ( mg/ kg); however, during LgA, males and females had more PCP deliveries compared with ShA. During LgA, males exceeded females in PCP deliveries, but females were higher than males in mg/ kg PCP intake. Also, PCP ( but not water) deliveries and mg/ kg PCP intake significantly increased from the first 3 days to the last 3 days of the 21-day LgA period in both males and females. The subsequent ShA FR 16 FR 16 performance did not differ by sex, but it was significantly elevated above the first ShA period in both sexes. The concentration-PR schedules and PCP intake ( mg/ kg) were significantly shifted upward during the second ( vs first) ShA period, and females' mg/ kg intake significantly exceeded males'.Conclusions: Male and female rhesus monkeys both showed escalation of PCP self-administration during LgA to PCP and during ShA that occurred after ( vs before) LgA. Both showed vertical upward shifts in the concentration x intake ( mg/ kg) function under the PR schedule, and females exceeded males on this measure. These findings with PCP and monkeys are consistent with vertical upward shifts of cocaine dose-response functions in previous escalation studies in male rats and reports of sex differences (F > M) during several other phases of drug abuse.