Rocha Angelica, Hart Nigel, Trujillo Keith A
Office for Training Research, and Education in the Sciences, California State University San Marcos, CA 92096, USA.
Office for Training Research, and Education in the Sciences, California State University San Marcos, CA 92096, USA; Department of Psychology, California State University San Marcos, CA 92096, USA.
Pharmacol Biochem Behav. 2017 Jun;157:24-34. doi: 10.1016/j.pbb.2017.04.007. Epub 2017 Apr 22.
Adolescence is a phase of development during which many physiological and behavioral changes occur, including increased novelty seeking and risk taking. In humans, this is reflected in experimentation with drugs. Research demonstrates that drug use that begins during adolescence is more likely to lead to addiction than drug use that begins later in life. Despite this, relatively little is known of the effects of drugs in adolescence, and differences in response between adolescents and adults. PCP and ketamine are popular club drugs, both possessing rewarding properties that could lead to escalating use. Drug sensitization (or reverse tolerance), which refers to an increase in an effect of a drug following repeated use, has been linked with the development of drug cravings that is a hallmark of addiction. The current work investigated the acute response and the development of sensitization to PCP and ketamine in adolescent and adult rats. Periadolescent Sprague-Dawley rats (30days or 38days of age), and young adults (60days of age) received PCP (6mg/kg IP) or ketamine (20mg/kg IP) once every three days, for a total of five drug injections. Adolescents and adults showed a stimulant response to the first injection of either drug, however the response was considerably greater in the youngest adolescents and lowest in the adults. With repeated administration, adults showed a robust escalation in activity that was indicative of the development of sensitization. Adolescents showed a flatter trajectory, with similar high levels of activity following an acute treatment and after five drug treatments. The results demonstrate important distinctions between adolescents and adults in the acute and repeated effects of PCP and ketamine.
青春期是一个发育阶段，在此期间会发生许多生理和行为变化，包括对新奇事物的追求增加和冒险行为。在人类中，这体现在药物试验上。研究表明，青春期开始使用药物比在生命后期开始使用药物更容易导致成瘾。尽管如此，人们对药物在青春期的影响以及青少年与成年人之间的反应差异了解相对较少。苯环己哌啶（PCP）和氯胺酮是常见的俱乐部毒品，两者都具有奖赏特性，可能导致用药量不断增加。药物敏化（或反向耐受）是指重复使用药物后药物效果增强，它与药物渴望的发展有关，而药物渴望是成瘾的一个标志。当前的研究调查了青春期和成年大鼠对PCP和氯胺酮的急性反应以及敏化的发展情况。青春期前后的斯普拉格-道利大鼠（30日龄或38日龄）和年轻成年大鼠（60日龄）每三天接受一次PCP（腹腔注射6mg/kg）或氯胺酮（腹腔注射20mg/kg），共注射五次药物。青少年和成年大鼠对首次注射任何一种药物均表现出兴奋反应，然而最年幼的青少年反应明显更大，而成年大鼠反应最小。随着药物的重复给药，成年大鼠的活动显著增强，这表明敏化的发展。青少年的活动轨迹较为平缓，急性给药后和五次药物治疗后的活动水平相似。结果表明，在PCP和氯胺酮的急性和重复效应方面，青少年和成年大鼠存在重要差异。
