Ukai M, Mitsunaga H
Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Methods Find Exp Clin Pharmacol. 2005 Nov;27(9):645-9. doi: 10.1358/mf.2005.27.9.939341.
The present study was carried out to determine the involvement of dopamine receptor subtypes D3 and D4, in the discriminative stimulus effects of cocaine in the rats trained to discriminate 10 mg/kg of cocaine from vehicle. The discriminative stimulus effects of cocaine (1-10 mg/kg) were dose-dependent. The dopamine D2 receptor agonist bromocriptine (1.25-20 mg/kg) and the dopamine D3 receptor agonist R(+)-7-OH-DPAT (0.0001-0.3 mg/kg) produced cocaine (10 mg/kg)-like discriminative stimulus effects. Both the dopamine D3 receptor antagonist GR103691 (1 mg/kg) and the dopamine D4 receptor antagonist L745870 (1 mg/kg) partially antagonized the discriminative stimulus effects of cocaine (10 mg/kg) and the cocaine (10 mg/kg)-like discriminative stimulus effects of R(+)-7-OH-DPAT (0.3 mg/kg). L745870 (0.001 mg/kg) inhibited the antagonistic effects of GR103691 (1 mg/kg) on the discriminative stimulus effects of cocaine (10 mg/kg), whereas the drug (0.001 mg/kg) enhanced the antagonistic effects of GR103691 (1 mg/kg) on the cocaine (10 mg/kg)-like discriminative stimulus effects of R(+)-7-OH-DPAT (0.3 mg/kg). GR103691 (1 mg/kg) in combination with L745870 (0.001 mg/kg) did not markedly affect the cocaine (10 mg/kg)-like discriminative stimulus effects of bromocriptine (20 mg/kg). These results suggest that the discriminative stimulus effects of cocaine are different from the cocaine-like discriminative stimulus effects of bromocriptine or R(+)-7-OH-DPAT, in terms of dopamine D3 and D4 receptors.
本研究旨在确定多巴胺受体亚型D3和D4在训练大鼠区分10 mg/kg可卡因与溶剂的过程中，对可卡因辨别性刺激效应的影响。可卡因（1 - 10 mg/kg）的辨别性刺激效应呈剂量依赖性。多巴胺D2受体激动剂溴隐亭（1.25 - 20 mg/kg）和多巴胺D3受体激动剂R(+)-7-OH-DPAT（0.0001 - 0.3 mg/kg）产生了与10 mg/kg可卡因相似的辨别性刺激效应。多巴胺D3受体拮抗剂GR103691（1 mg/kg）和多巴胺D4受体拮抗剂L745870（1 mg/kg）均部分拮抗了10 mg/kg可卡因的辨别性刺激效应以及R(+)-7-OH-DPAT（0.3 mg/kg）产生的类似10 mg/kg可卡因的辨别性刺激效应。L745870（0.001 mg/kg）抑制了GR103691（1 mg/kg）对10 mg/kg可卡因辨别性刺激效应的拮抗作用，而该药物（0.001 mg/kg）增强了GR103691（1 mg/kg）对R(+)-7-OH-DPAT（0.3 mg/kg）产生的类似10 mg/kg可卡因辨别性刺激效应的拮抗作用。GR103691（1 mg/kg）与L745870（0.001 mg/kg）联合使用并未显著影响溴隐亭（20 mg/kg）产生的类似10 mg/kg可卡因的辨别性刺激效应。这些结果表明，就多巴胺D3和D4受体而言，可卡因的辨别性刺激效应与溴隐亭或R(+)-7-OH-DPAT产生的类似可卡因的辨别性刺激效应不同。
