Behavioral and neurochemical responses to cocaine in periadolescent and adult rats
Behavioral and neurochemical responses to cocaine in periadolescent and adult rats
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DOI：
10.1038/sj.npp.1301130
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发表时间：
2007-03-01
影响因子：
7.6
通讯作者：
Parsons, Loren H.
中科院分区：
文献类型：
--
作者：
Frantz, Kyle J.;O'Dell, Laura E.;Parsons, Loren H.
尽管人类青少年使用娱乐性药物是一个众所周知且长期存在的问题，但对于青少年与成年动物对滥用物质的行为和生理反应的差异知之甚少。本研究比较了精神运动兴奋剂可卡因对青春期（出生后 37 - 52 天）和成年（出生后 75 - 90 天）雄性 Wistar 大鼠的影响。急性和重复注射可卡因（0、10 或 20 mg/kg 可卡因，腹膜内 (i.p.)，四次注射，间隔 5 天）后记录运动和运动定型。在 14 天内，对两个剂量组（类似于 0.37 或 0.74 mg/kg/输注）自发获得静脉 (i.v.) 可卡因自我给药进行了研究。使用体内微透析在基础条件下（无净通量法）和可卡因给药后（类似于 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大鼠与成年大鼠对急性可卡因不敏感的报道部分一致。总体而言，青春期儿童的活动量低于成年人。此外，成年大鼠在重复注射10 mg/kg可卡因后表现出显着的运动致敏作用，而青春期大鼠需要高剂量的20 mg/kg可卡因才能表现出致敏作用。两个年龄组都没有表现出对运动刻板印象的敏感性。在可卡因自我给药或基础或可卡因刺激的伏核多巴胺的获得方面没有观察到与年龄相关的差异。这些实验意味着可卡因的运动激活和增强作用之间存在发育分离。各年龄段多巴胺水平的相似性表明，针对可卡因的年龄特异性运动反应不是由伏隔核中的多巴胺介导的。
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 ( similar to 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 ( similar to 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.