Caster Joseph M, Walker Q David, Kuhn Cynthia M
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Room 100-B, Research Park Building 2, P.O. Box 3813, Durham, NC 27710, USA.
Psychopharmacology (Berl). 2005 Dec;183(2):218-25. doi: 10.1007/s00213-005-0159-4. Epub 2005 Nov 9.
Most lifelong drug addiction in humans originates during adolescence. Important structural and functional changes in the brain occur during adolescence, but there has been little direct study of how this impacts on drug abuse vulnerability. An emerging literature suggests that adolescents exhibit different behavioral responses to single doses of several addictive drugs, including ethanol, amphetamine, and cocaine. However, few studies have explored behavioral responses to the repeated dosing that is characteristic of human abuse of these substances.
We have investigated age-related behavioral responses to acute "binge" cocaine treatment between adults and adolescents.
Adolescent rats displayed an exaggerated behavioral response to cocaine administered in two different binge patterns. Total locomotion after cocaine administration was the same in adolescents and adults. However, adolescent rats engaged in more intense stereotypic behaviors, including paw treading, head weaving, and focused sniffing than adult rats. These differences were observable following a modest dose of cocaine and became more robust following subsequent doses within a binge. Cocaine [corrected] brain levels were not significantly different between age groups during any of the exposure sessions.
These findings suggest that equivalent tissue concentrations of cocaine produce a greater behavioral response in young rats, and that adolescent animals display an apparent form of intrabinge sensitization.
人类大多数终身药物成瘾始于青春期。青春期大脑会发生重要的结构和功能变化,但关于这如何影响药物滥用易感性的直接研究很少。新出现的文献表明,青少年对包括乙醇、苯丙胺和可卡因在内的几种成瘾药物的单剂量表现出不同的行为反应。然而,很少有研究探讨对这些物质人类滥用特征的重复给药的行为反应。
我们研究了成年和青少年对急性“暴饮暴食”可卡因治疗的年龄相关行为反应。
青春期大鼠对以两种不同暴饮暴食模式给予的可卡因表现出夸张的行为反应。可卡因给药后的总运动在青少年和成年大鼠中相同。然而,青春期大鼠比成年大鼠表现出更强烈的刻板行为,包括爪踏、头部摆动和专注嗅探。这些差异在给予适量可卡因后即可观察到,并且在暴饮暴食期间后续剂量后变得更加明显。在任何暴露阶段,各年龄组之间的可卡因脑内水平均无显著差异。
这些发现表明,可卡因的等效组织浓度在幼鼠中产生更大的行为反应,并且青春期动物表现出一种明显的暴饮暴食内敏化形式。