Frantz Kyle J, O'Dell Laura E, Parsons Loren H
Department of Biology, Georgia State University, Atlanta, GA 30302-4010, USA.
Neuropsychopharmacology. 2007 Mar;32(3):625-37. doi: 10.1038/sj.npp.1301130. Epub 2006 Jun 21.
Although recreational drug use by human adolescents is a well-known and long-standing problem, relatively little is known regarding differences in behavioral and physiological responses to abused substances in adolescent vs adult animals. The present study compared effects of the psychomotor stimulant, cocaine, in periadolescent (postnatal days 37-52) and adult (postnatal days 75-90) male Wistar rats. Locomotion and motor stereotypy were recorded after acute and repeated cocaine injections (0, 10, or 20 mg/kg cocaine, intraperitoneal (i.p.), four injections spaced 5 days apart). Spontaneous acquisition of intravenous (i.v.) cocaine self-administration was investigated in two dose groups ( approximately 0.37 or 0.74 mg/kg/infusion) over 14 days. Dopamine levels in the nucleus accumbens were recorded under basal conditions (no net flux method) and after cocaine administration ( approximately 0.37, 0.74, and 2.92 mg/kg/i.v. infusion or 20 mg/kg i.p.) using in vivo microdialysis. The locomotor data are in partial agreement with previous reports of hyposensitivity to acute cocaine in periadolescent vs adult rats; periadolescents were less active overall than adults. Moreover, adult rats exhibited significant locomotor sensitization after repeated injection of 10 mg/kg cocaine, whereas periadolescents required the high dose of 20 mg/kg cocaine to demonstrate sensitization. Neither age group showed sensitization of motor stereotypies. No age-related difference was observed in acquisition of cocaine self-administration, or in basal or cocaine-stimulated nucleus accumbens dopamine. These experiments imply a developmental dissociation between the motor activating and reinforcing effects of cocaine. Similarities in dopamine levels across age groups suggest that age-specific motor responses to cocaine are not mediated by dopamine in the nucleus accumbens.
尽管人类青少年使用消遣性药物是一个广为人知且长期存在的问题，但对于青少年与成年动物在对滥用物质的行为和生理反应方面的差异，我们了解得相对较少。本研究比较了精神运动兴奋剂可卡因对青春期前后（出生后第37 - 52天）和成年（出生后第75 - 90天）雄性Wistar大鼠的影响。在急性和重复注射可卡因（0、10或20 mg/kg可卡因，腹腔注射（i.p.），共四次注射，间隔5天）后记录运动和运动刻板行为。在两个剂量组（约0.37或0.74 mg/kg/输注）中，对静脉注射（i.v.）可卡因自我给药的自发获取情况进行了为期14天的研究。使用体内微透析技术，在基础条件下（无净通量法）以及给予可卡因后（约0.37、0.74和2.92 mg/kg/i.v.输注或20 mg/kg i.p.）记录伏隔核中的多巴胺水平。运动数据与之前关于青春期前后大鼠与成年大鼠对急性可卡因低敏感性的报道部分一致；青春期前后大鼠总体上比成年大鼠活动少。此外，成年大鼠在重复注射10 mg/kg可卡因后表现出显著的运动致敏，而青春期前后大鼠需要20 mg/kg的高剂量可卡因才能表现出致敏。两个年龄组均未表现出运动刻板行为的致敏。在可卡因自我给药的获取、基础或可卡因刺激的伏隔核多巴胺方面，未观察到与年龄相关的差异。这些实验表明可卡因的运动激活和强化作用在发育过程中存在分离。各年龄组多巴胺水平的相似性表明，年龄特异性的对可卡因的运动反应不是由伏隔核中的多巴胺介导的。
