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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Analysis of D2 and D3 receptor-selective ligands in rats trained to discriminate cocaine from saline.
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Analysis of D2 and D3 receptor-selective ligands in rats trained to discriminate cocaine from saline.

机译：训练区分盐水中可卡因的大鼠中D2和D3受体选择性配体的分析。

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This study examined the role of dopamine D3 receptors in the stimulus generalization produced by 7-OH-DPAT and PD 128907 in rats trained to discriminate cocaine from saline. Twelve male Sprague-Dawley rats were trained to discriminate cocaine (10 mg/kg) from saline in a two-choice operant procedure using a FR20 schedule of water reinforcement. Stimulus generalization tests were administered with the D3-preferring agonists (+/-)-7-OH-DPAT (0.01-0.3 mg/kg), (+)-7-OH-DPAT (0.01-0.3 mg/kg), and PD 128907 (0.01-0.3 mg/kg), and the selective D2 agonist PNU-39156 (0.01-0.3 mg/kg). Complete generalization to cocaine was observed with (+/-)-7-OH-DPAT at doses that markedly suppressed response rate. Only partial stimulus generalization was observed with (+)-7-OH-DPAT and PD 128907 when these compounds were administered intraperitoneally, although subcutaneous injections of these compounds produced complete substitution. Response rate was also significantly reduced by these compounds. The selective D2 agonist, PNU-91356 also fully substituted for the cocaine cue and suppressed response rate in a dose-dependent manner. To ascertain the importance of D3 receptor actions in the stimulus generalization produced by (+/-)-7-OH-DPAT (0.1 mg/kg) and PD-128907 (0.3 mg/kg), the fairly selective D3 antagonist, PNU-99194A (2.5-20 mg/kg) was also tested in combination with these compounds. Although PNU-99194A partially attenuated the stimulus generalization produced by (+/-)-7-OH-DPAT, it failed to block PD-128907 substitution for cocaine. These results indicate at least some involvement of D3 receptors in the stimulus effects of (+/-)-7-OH-DPAT, although further investigations are clearly warranted. The present results also suggest that the cue properties of cocaine may be dissociated from the locomotor activating effects of this drug, because D3/D2 receptor agonists suppress locomotor activity but produce stimulus generalization to cocaine.
机译：这项研究检查了多巴胺D3受体在7-OH-DPAT和PD 128907产生的刺激性泛化中的作用，该大鼠受过训练以从盐水中区分可卡因。训练了十二只雄性Sprague-Dawley大鼠，使用FR20补水时间表，通过二选一操作程序从盐水中区分可卡因（10 mg / kg）。给予D3激动剂（+/-）-7-OH-DPAT（0.01-0.3 mg / kg），（+）-7-OH-DPAT（0.01-0.3 mg / kg）和PD 128907（0.01-0.3 mg / kg）和选择性D2激动剂PNU-39156（0.01-0.3 mg / kg）。用（+/-）-7-OH-DPAT在可明显抑制应答率的剂量下观察到可卡因的完全泛化。尽管皮下注射这些化合物可产生完全取代，但腹膜内给予（+）-7-OH-DPAT和PD 128907时，仅观察到部分刺激。这些化合物的反应率也显着降低。选择性D2激动剂PNU-91356还以剂量依赖性方式完全替代了可卡因提示并抑制了响应率。为了确定D3受体作用在（+/-）-7-OH-DPAT（0.1 mg / kg）和PD-128907（0.3 mg / kg）（相当选择性的D3拮抗剂，PNU-还与这些化合物联合测试了99194A（2.5-20 mg / kg）。尽管PNU-99194A部分减弱了（+/-）-7-OH-DPAT产生的刺激普遍性，但它未能阻止PD-128907替代可卡因。这些结果表明，D3受体至少参与（+/-）-7-OH-DPAT的刺激作用，尽管显然需要进一步研究。目前的结果还表明，可卡因的提示特性可能与该药物的运动激活作用无关，因为D3 / D2受体激动剂抑制运动活性，但产生可卡因刺激。

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