Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Japan.
Addict Biol. 2012 Nov;17(6):949-55. doi: 10.1111/j.1369-1600.2010.00257.x. Epub 2010 Nov 4.
Substitutions of the dopamine D(2) or D(3) receptor agonists for the discriminative stimulus effect induced by U-50,488H, methamphetamine (METH) and cocaine in rats were examined. The D(2) receptor agonist R-propylnorapomorphine [(-)-NPA] failed to substitute for U-50,488H cue, while the D(3) receptor-preferred agonist (+/-)-7-hydroxy-dipropylaminotetralin hydrobromide (7-OH-DPAT) produced dose-related increases in drug-appropriate responding up to 0.03 mg/kg, which fully substituted. At doses greater than 0.03 mg/kg of 7-OH-DPAT, there was a dose-dependent decrease in the percentage of responses on the U-50,488H-appropriate lever. Furthermore (-)-NPA and 7-OH-DPAT at high doses substituted for the discriminative stimulus effect induced by both METH and cocaine, indicating that 7-OH-DPAT at high doses may interact with D(2) receptors. These results suggest that the stimulation of D(2) receptor may be critical for the production of the discriminative stimulus effect induced by METH and cocaine, whereas the stimulation of D(3) receptor may contribute to the production of the U-50,488H cue.
研究了多巴胺 D(2)或 D(3)受体激动剂替代 U-50,488H、甲基苯丙胺（METH）和可卡因在大鼠中诱导的辨别刺激效应。D(2)受体激动剂 R-丙基norapomorphine [(-)-NPA]未能替代 U-50,488H 线索，而 D(3)受体偏好激动剂 (+/-)-7-羟基-二丙基氨基四氢萘氢溴酸盐（7-OH-DPAT）则产生与剂量相关的药物适当反应增加，最高可达 0.03mg/kg，完全替代。在 7-OH-DPAT 的剂量大于 0.03mg/kg 时，在 U-50,488H 适当杠杆上的反应百分比呈剂量依赖性下降。此外，(-)-NPA 和 7-OH-DPAT 在高剂量下替代 METH 和可卡因诱导的辨别刺激效应，表明 7-OH-DPAT 在高剂量下可能与 D(2)受体相互作用。这些结果表明，D(2)受体的刺激对于 METH 和可卡因诱导的辨别刺激效应的产生可能是至关重要的，而 D(3)受体的刺激可能有助于 U-50,488H 线索的产生。
