Juarez-Portilla C, Kim R D, Robotham M, Tariq M, Pitter M, LeSauter J, Silver R
Centro de Investigaciones Biomédicas, Universidad Veracruzana, Veracruz, Mexico.
Department of Psychology, Columbia University, New York, NY, 10027, USA.
Psychopharmacology (Berl). 2017 Mar;234(5):739-747. doi: 10.1007/s00213-016-4510-8. Epub 2016 Dec 27.
The abuse of the psychostimulant methamphetamine (MA) is associated with substantial costs and limited treatment options. To understand the mechanisms that lead to abuse, animal models of voluntary drug intake are crucial.
We aimed to develop a protocol to study long-term non-invasive voluntary intake of MA in mice.
Mice were maintained in their home cages and allowed daily 1 h access to an attached tunnel leading to a test chamber in which nebulized MA was available. Restated, if they went to the nebulizing chamber, they self-administered MA by inhalation. This protocol was compared to injected and to imposed exposure to nebulized MA, in a series of seven experiments.
We established a concentration of nebulized MA at which motor activity increases following voluntary intake resembled that following MA injection and imposed inhalation. We found that mice regulated their exposure to MA, self-administering for shorter durations when concentrations of nebulized MA were increased. Mice acquire the available MA by repeatedly running in and out of the nebulizing chamber for brief bouts of intake. Such exposure to nebulized MA elevated plasma MA levels. There was limited evidence of sensitization of locomotor activity. Finally, blocking access to the wheel did not affect time spent in the nebulizing chamber.
We conclude that administration of MA by nebulization is an effective route of self-administration, and our new protocol represents a promising tool for examining the transitions from first intake to long-term use and its behavioral and neural consequences in a non-invasive protocol.
精神刺激药物甲基苯丙胺（MA）的滥用造成了巨大代价且治疗选择有限。为了解导致滥用的机制，自愿药物摄入的动物模型至关重要。
我们旨在制定一种方案来研究小鼠长期非侵入性自愿摄入MA的情况。
将小鼠饲养在其笼舍中，每天允许它们有1小时进入连接到测试室的通道，测试室内有雾化的MA。换句话说，如果它们进入雾化室，就通过吸入自行摄入MA。在一系列七个实验中，将该方案与注射以及强制暴露于雾化MA的情况进行了比较。
我们确定了一种雾化MA的浓度，在此浓度下，自愿摄入后运动活动的增加与注射MA和强制吸入后的情况相似。我们发现小鼠会调节它们对MA的接触，当雾化MA的浓度增加时，它们自行摄入的持续时间会缩短。小鼠通过反复进出雾化室进行短暂的摄入来获取可用的MA。这种对雾化MA的接触会提高血浆MA水平。运动活动致敏的证据有限。最后，阻止使用轮子并不影响在雾化室中花费的时间。
我们得出结论，雾化给药MA是一种有效的自行给药途径，我们的新方案是一种有前景的工具，可用于在非侵入性方案中研究从首次摄入到长期使用的转变及其行为和神经后果。
