Modulatory role of D-1 and D-2 dopamine receptor subtypes in nociception in mice

Abstract

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.