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多巴胺能动员引发的行为垂直化在C57BL/6J和DBA/2J小鼠之间存在质的差异。

Verticalization of behavior elicited by dopaminergic mobilization is qualitatively different between C57BL/6J and DBA/2J mice.

作者信息

Tirelli E, Witkin J M

机构信息

Psychobiology Section, Addiction Research Center, National Institute on Drug Abuse, Baltimore, Maryland.

出版信息

Psychopharmacology (Berl). 1994 Oct;116(2):191-200. doi: 10.1007/BF02245062.

Abstract

Behavioral effects of dopaminergic stimulation were evaluated in C57BL/6J mice and compared to the effects occurring in DBA/2J mice, an inbred strain with reduced densities of striatal dopamine receptors. Effects of apomorphine (0.5-64 mg/kg) alone and in combination with cocaine (30 mg/kg) were assessed using a time-sampling technique that classified climbing and leaning in separate categories. Locomotion was also assessed in a separate experiment. Climbing occurred in DBA/2J mice only at doses of apomorphine that were 16 times higher than the smallest effective dose in C57BL/6J mice; nevertheless, relative to baseline values, effects were fairly comparable. By contrast, whereas DBA/2J mice showed dose-dependent leaning under apomorphine, C57BL/6J mice exhibited little leaning even at doses not producing climbing, and only after the highest apomorphine dose was leaning significantly increased. Apomorphine was equipotent in inducing gnawing across strains, although somewhat less efficacious in DBA/2J mice. When given alone, cocaine produced significant climbing, but not leaning or gnawing, in either strain. Whereas cocaine potentiated apomorphine-induced climbing and gnawing in both strains, apomorphine-induced leaning was not consistently changed by cocaine in either strain. These effects were not indirectly due to hyperkinesia, since neither apomorphine alone nor apomorphine and cocaine in combination was stimulant; apomorphine alone reduced locomotor activity and attenuated cocaine-induced hyperkinesia. The present data do not support a unitary, purely quantitative, account of insensitivity to dopaminergic stimulation based upon low densities of striatal dopamine receptors in DBA/2J mice. Rather, this constellation of results is suggestive of qualitative interstrain dissimilarities in dopaminergic responsiveness that could reflect organizational differences in receptor populations.

摘要

在C57BL/6J小鼠中评估了多巴胺能刺激的行为效应,并与DBA/2J小鼠(一种纹状体多巴胺受体密度降低的近交系)中出现的效应进行了比较。使用时间采样技术评估单独使用阿扑吗啡(0.5 - 64 mg/kg)以及与可卡因(30 mg/kg)联合使用时的效应,该技术将攀爬和倾斜分为不同类别。在另一个单独的实验中也评估了运动能力。DBA/2J小鼠仅在阿扑吗啡剂量比C57BL/6J小鼠中最小有效剂量高16倍时才出现攀爬;然而,相对于基线值,效应相当可比。相比之下,虽然DBA/2J小鼠在阿扑吗啡作用下表现出剂量依赖性倾斜,但C57BL/6J小鼠即使在未产生攀爬的剂量下也几乎没有倾斜,只有在最高阿扑吗啡剂量后倾斜才显著增加。阿扑吗啡在诱导两品系小鼠啃咬方面效力相当,尽管在DBA/2J小鼠中效力稍低。单独给予时,可卡因在两种品系小鼠中均产生显著攀爬,但不产生倾斜或啃咬。虽然可卡因增强了两种品系小鼠中阿扑吗啡诱导的攀爬和啃咬,但阿扑吗啡诱导的倾斜在两种品系小鼠中均未因可卡因而持续改变。这些效应并非间接由运动亢进引起,因为单独的阿扑吗啡以及阿扑吗啡与可卡因联合使用均无刺激作用;单独的阿扑吗啡降低了运动活性并减弱了可卡因诱导的运动亢进。目前的数据不支持基于DBA/2J小鼠纹状体多巴胺受体低密度对多巴胺能刺激不敏感的单一、纯粹定量的解释。相反,这一系列结果表明多巴胺能反应性存在品系间的质性差异,这可能反映了受体群体的组织差异。

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