Verma A, Kulkarni S K
Pharmacology Division, Department of Pharmaceutical Sciences, Panjab University, Chandigarh-160014, India.
J Psychopharmacol. 1993 Jan;7(3):270-5. doi: 10.1177/026988119300700306.
The role of D-1 and D-2 dopamine (DA) receptors in nociception in naive as well as reserpinized mice and the modulation of the nociceptive action of morphine or naloxone by the selective D-1 and D-2 DA agonists, was investigated in mice. The D-2 DA agonists, B-HT 920 and bromocriptine produced an anti-nociceptive effect in naive mice and reversed the hyperalgesic effect of reserpine (2 mg/kg, 4 h prior) pre-treatment. The D-1 DA agonist, SKF 38393 (5 mg/kg) failed to alter the nociceptive responsiveness of naive and reserpinized mice. Apomorphine, a mixed D-1/D-2 DA agonist, produced significant analgesia in naive mice and also reversed reserpine-induced hyperalgesia. SKF 38393 (5 mg/kg) enhanced the anti-nociceptive effect of B-HT 920 (0.1 mg/kg) in naive and reserpine-pre-treated mice. The anti-nociceptive response of morphine (5 mg/kg) was enhanced by B-HT 920 while SKF 38393 reduced the same. Apomorphine (0.5 mg/kg) or the combination of B-HT 920 (0.1 mg/kg) and SKF 38393 (5 mg/kg) failed to enhance the anti-nociceptive effect of morphine. Reserpine (2 mg/kg, 4 h prior) pre-treatment significantly reduced the anti-nociceptive effect of morphine. Similarly, the hyperalgesic action of naloxone (20 mg/kg) was reversed by B-HT 920, bromocriptine and apomorphine but not by SKF 38393. The reversal of the hyperalgesic action of naloxone by B-HT 920 was blocked by pre-treatment with haloperidol (0.5 mg/kg) and sulpiride (100 mg/kg). SKF 38393 (5 mg/kg) failed to potentiate the reversal action of B-HT 920 against naloxone. These data suggest a predominant role of D-2 DA receptors in anti-nociception and the possibility of the existence of an interlink between the DAergic and opioid systems.
在小鼠中研究了D1和D2多巴胺（DA）受体在未处理以及利血平化小鼠伤害感受中的作用，以及选择性D1和D2 DA激动剂对吗啡或纳洛酮伤害性作用的调节。D2 DA激动剂B-HT 920和溴隐亭在未处理小鼠中产生抗伤害感受作用，并逆转了利血平（2mg/kg，提前4小时）预处理的痛觉过敏作用。D1 DA激动剂SKF 38393（5mg/kg）未能改变未处理和利血平化小鼠的伤害性反应性。阿扑吗啡，一种混合的D1/D2 DA激动剂，在未处理小鼠中产生显著的镇痛作用，并且也逆转了利血平诱导的痛觉过敏。SKF 38393（5mg/kg）增强了B-HT 920（0.1mg/kg）在未处理和利血平预处理小鼠中的抗伤害感受作用。B-HT 920增强了吗啡（5mg/kg）的抗伤害感受反应，而SKF 38393则降低了该反应。阿扑吗啡（0.5mg/kg）或B-HT 920（0.1mg/kg）与SKF 38393（5mg/kg）的组合未能增强吗啡的抗伤害感受作用。利血平（2mg/kg，提前4小时）预处理显著降低了吗啡的抗伤害感受作用。同样，纳洛酮（20mg/kg）的痛觉过敏作用被B-HT 920、溴隐亭和阿扑吗啡逆转，但未被SKF 38393逆转。B-HT 920对纳洛酮痛觉过敏作用的逆转被氟哌啶醇（0.5mg/kg）和舒必利（100mg/kg）预处理阻断。SKF 38393（5mg/kg）未能增强B-HT 920对纳洛酮的逆转作用。这些数据表明D2 DA受体在抗伤害感受中起主要作用，并且提示多巴胺能系统和阿片系统之间可能存在相互联系。
