Mikkola J A, Honkanen A, Piepponen T P, Kiianmaa K, Ahtee L
Department of Pharmacy, University of Helsinki, Finland.
Naunyn Schmiedebergs Arch Pharmacol. 2001 Feb;363(2):209-14. doi: 10.1007/s002100000367.
Modulation of striatal dopamine (DA) release by acute or repeated cocaine treatment was studied in the nucleus accumbens and caudate-putamen of alcohol-preferring (AA, Alko Alcohol) and alcohol-avoiding (ANA, Alko Non-Alcohol) rats. Cocaine (5-10 mg/kg i.p.) was administered daily for 4 days and the concentrations of extracellular DA measured by in vivo microdialysis on days 1 and 4 in the freely moving rats. The first administration of cocaine increased DA concentration similarly in rats of both lines in both the nucleus accumbens and caudate-putamen. On the 4th day, the effect of cocaine was significantly larger in the nucleus accumbens of AA than in that of ANA rats, whereas no such enhanced effect of cocaine was found in the caudate-putamen of either line. The results suggest that mesolimbic DA release in response to cocaine is sensitized more readily in AA than in ANA rats, which would not only render the former more susceptible to alcohol, but to other drugs of abuse, and might explain our previous findings that AA rats are more susceptible to psychomotor sensitization than ANA rats.
在偏好酒精的(AA,阿尔科酒精型)和回避酒精的(ANA,阿尔科非酒精型)大鼠的伏隔核和尾状核壳中,研究了急性或反复给予可卡因对纹状体多巴胺(DA)释放的调节作用。每天腹腔注射可卡因(5 - 10毫克/千克),持续4天,并在第1天和第4天通过体内微透析测量自由活动大鼠的细胞外DA浓度。首次给予可卡因后,两品系大鼠的伏隔核和尾状核壳中的DA浓度均有类似升高。在第4天,可卡因对AA大鼠伏隔核的作用显著大于对ANA大鼠的作用,而在两品系大鼠的尾状核壳中均未发现可卡因的这种增强作用。结果表明,与ANA大鼠相比,AA大鼠对可卡因反应的中脑边缘DA释放更容易产生敏感化,这不仅会使前者对酒精更易感,而且对其他滥用药物也更易感,这可能解释了我们之前的发现,即AA大鼠比ANA大鼠更容易产生精神运动敏感化。