Lynch Wendy J, Taylor Jane R
Department of Psychiatry, Yale University, New Haven, CT 06516, USA.
Neuropsychopharmacology. 2004 May;29(5):943-51. doi: 10.1038/sj.npp.1300389.
Although more men than women are addicted to cocaine, it has been suggested that women may have an accelerated transition to addiction, and that once addicted they may be more vulnerable to relapse. Here we investigate the effects of extended access to cocaine under a 24-h/day discrete trial procedure on patterns of intake and subsequent motivation to use cocaine as assessed by responding under a progressive-ratio schedule in male and female rats. Rats were initially trained to self-administer cocaine (1.5 mg/kg/infusion) under a fixed-ratio 1 schedule until acquisition occurred, and then responding was assessed under a progressive schedule for three sessions. Subsequently, rats had 24-h access to intravenous cocaine infusions (1.5 mg/kg) that were available in discrete trials (4, 10 min trials/h) for 7 consecutive days. At 10 days after the last discrete trial session, responding was reassessed under a progressive-ratio schedule for three additional sessions to investigate changes in motivation to obtain cocaine. Prior to cocaine self-administration under the 24-h access discrete trial procedure, males and females did not differ on cocaine self-administration under the fixed-ratio or progressive-ratio schedules. However, sex differences emerged under the 24-h access discrete trial procedure with females self-administering higher levels of cocaine, for longer initial periods of time, and showing a greater disruption in the diurnal control over intake than did males. Additionally, following a 10-day forced abstinence period, females responded at higher levels under the progressive-ratio schedule to obtain cocaine infusions than did males. These findings suggest that extended access to cocaine under the discrete trial cocaine self-administration procedure produces sex-dependent patterns of intake and sex-specific changes in motivation to obtain cocaine as measured by progressive-ratio responding.
虽然对可卡因上瘾的男性多于女性，但有人认为女性可能会更快地转变为成瘾状态，而且一旦成瘾，她们可能更容易复发。在此，我们研究了在每天24小时的离散试验程序下延长获取可卡因的机会对摄入模式以及随后使用可卡因的动机的影响，该动机通过雄性和雌性大鼠在累进比率时间表下的反应来评估。大鼠最初在固定比率1的时间表下接受训练以自我给药可卡因（1.5毫克/千克/注射），直到习得发生，然后在累进时间表下评估三次会话的反应。随后，大鼠有24小时的静脉注射可卡因（1.5毫克/千克）的机会，该机会在离散试验（每小时4次，每次10分钟的试验）中连续7天可用。在最后一次离散试验会话后的第10天，在累进比率时间表下再次评估反应，进行另外三次会话，以研究获取可卡因动机的变化。在24小时获取离散试验程序下进行可卡因自我给药之前，雄性和雌性在固定比率或累进比率时间表下的可卡因自我给药方面没有差异。然而，在24小时获取离散试验程序下出现了性别差异，雌性自我给药的可卡因水平更高，初始时间更长，并且与雄性相比，在摄入的昼夜控制方面表现出更大的干扰。此外，在10天的强制禁欲期后，雌性在累进比率时间表下为获得可卡因注射的反应水平高于雄性。这些发现表明，在离散试验可卡因自我给药程序下延长获取可卡因的机会会产生与性别相关的摄入模式以及通过累进比率反应测量的获取可卡因动机的性别特异性变化。
