Hamamura T, Fibiger H C
Department of psychiatry, University of British Columbia, Vancouver, Canada.
Eur J Pharmacol. 1993 Jun 11;237(1):65-71. doi: 10.1016/0014-2999(93)90094-x.
This study examined the extent to which chronic d-amphetamine administration sensitizes animals to some behavioral and neurochemical effects of foot shock stress. Rats received daily injections of saline for 14 days or d-amphetamine (2 mg/kg 7 days and 4 mg/kg 7 days). After a 7 day drug abstinent period, extracellular dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid concentrations were measured in the medial prefrontal cortex using in vivo microdialysis in freely moving rats. The behavioral responses to mild foot shock stress were enhanced in the d-amphetamine-pretreated subjects. Concomitant with this behavioral sensitization, d-amphetamine-pretreated subjects showed greater stress-induced increases in extracellular dopamine in the medial prefrontal cortex than in controls. d-Amphetamine (2 mg/kg)-induced stereotyped behavior was also enhanced in the amphetamine-pretreated animals compared to controls; however, d-amphetamine-induced increases in extracellular dopamine in the medial prefrontal cortex were not enhanced in the amphetamine-pretreated group. These results suggest that the mesocortical dopaminergic system is involved in cross-sensitization between d-amphetamine and stress, but not in d-amphetamine-induced behavioral sensitization.
本研究考察了长期给予d-苯丙胺使动物对足部电击应激的某些行为和神经化学效应产生敏感的程度。大鼠连续14天每日注射生理盐水，或注射d-苯丙胺（7天2mg/kg，7天4mg/kg）。在7天的药物戒断期后，使用体内微透析技术在自由活动的大鼠内侧前额叶皮质中测量细胞外多巴胺、3,4-二羟基苯乙酸和高香草酸的浓度。在经d-苯丙胺预处理的动物中，对轻度足部电击应激的行为反应增强。与这种行为敏感化相伴的是，经d-苯丙胺预处理的动物在内侧前额叶皮质中，应激诱导的细胞外多巴胺增加幅度大于对照组。与对照组相比，经苯丙胺预处理的动物中，d-苯丙胺（2mg/kg）诱导的刻板行为也增强；然而，在经苯丙胺预处理的组中，d-苯丙胺诱导的内侧前额叶皮质细胞外多巴胺增加并未增强。这些结果表明，中脑皮质多巴胺能系统参与了d-苯丙胺与应激之间的交叉敏感化，但不参与d-苯丙胺诱导的行为敏感化。
