INBRED RAT STRAIN COMPARISONS INDICATE DIFFERENT SITES OF ACTION FOR COCAINE AND AMPHETAMINE LOCOMOTOR STIMULANT EFFECTS
INBRED RAT STRAIN COMPARISONS INDICATE DIFFERENT SITES OF ACTION FOR COCAINE AND AMPHETAMINE LOCOMOTOR STIMULANT EFFECTS
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DOI：
10.1007/bf02245649
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发表时间：
1991-01-01
影响因子：
3.4
通讯作者：
GOLDBERG, SR
中科院分区：
文献类型：
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作者：
GEORGE, FR;PORRINO, LJ;GOLDBERG, SR
可卡因和安非他明产生几种行为效应，最显著的是运动刺激。生物化学方面，证据表明多巴胺能系统的具体参与，虽然不一定相同的网站，在介导可卡因和安非他明诱导的运动刺激。本研究探讨了可卡因或安非他明对ACI，F344，LEW和NBR近交系大鼠自发活动的影响。在所有菌株中发现两种药物的自发活动呈剂量依赖性增加。然而，大的效力和疗效差异被发现。此外，显着的菌株药物相互作用被发现，在菌株的排名顺序为刺激响应两种药物是不相同的。由于纹状体多巴胺能神经元的影响自发活动，我们还评估了配体亲和力和受体密度的多巴胺转运蛋白和多巴胺能D1和D2受体在纹状体组织从这些相同的大鼠品系。这些受体结合参数无差异，发现这些发现支持的结论，这两种药物产生的运动刺激剂的作用，通过不同的网站，并在行为水平上，这些药物的遗传差异，似乎不介导的纹状体多巴胺能网站的结构或数量的差异显着。然而，遗传学方法的进一步使用可能有助于确定这些广泛使用的兴奋剂药物的具体作用部位。
Cocaine and amphetamine produce several behavioral effects, most notably locomotor stimulation. Biochemically, evidence suggests specific involvement of dopaminergic systems, although not necessarily identical sites, in mediating cocaine- and amphetamine-induced locomotor stimulation. This study examined the effects of cocaine or amphetamine on locomotor activity in rats from the ACI, F344, LEW and NBR inbred strains. Dose-dependent increases in locomotor activity were found for both drugs in all strains. However, large potency and efficacy differences were found. Further, significant strain by drug interactions were found, in that the strain rank order for stimulant response to the two drugs was not identical. Since striatal dopaminergic neurons influence locomotor activity, we also assessed ligand affinity and receptor density of dopamine transporters and dopaminergic D1 and D2 receptors in striatal tissue from these same strains of rats. No differences in these receptor binding parameters were found. These findings support the conclusion that these two drugs produce their locomotor stimulant effects through different sites of action, and that genetic differences in response to these drugs at the behavioral level do not appear to be mediated significantly by differences in structure or number of striatal dopaminergic sites. The further use of genetic methods, however, may aid in determining the specific sites of action of these widely used stimulant drugs.