Role of D1/D2 dopamine and N-methyl-D-aspartate (NMDA) receptors in morphine tolerance and dependence in mice.

Chronic treatment with the dopamine (DA) agonist B-HT 920 (0.25-1 mg/kg) or bromocriptine (1 mg/kg) followed by morphine (10 mg/kg) on days 1-9 prevented the development of tolerance to the antinociceptive effect of morphine as measured by the tail-flick test in mice, but failed to suppress the development of morphine dependence as assessed by naloxone (2 mg/kg)-precipitated withdrawal jumps on day 10 of testing. Repeated administration of SKF 38393 (5 mg/kg) followed by morphine for 9 days significantly reduced naloxone-precipitated jumps on day 10 but failed to produce any significant change in tail-flick latency from the saline-pretreated group of mice on days 9 and 10 of testing. Repeated administration of B-HT 920 or bromocriptine enhanced the ability of MK-801 to attenuate the development of morphine tolerance and dependence while SKF 38393 failed to do so. The above data suggest a preferential role of D2 DA receptors in morphine tolerance and D1 receptors in the development of morphine dependence. D2 DA receptor stimulation may also play an important role in enhancing the effectiveness of MK-801 in the treatment of opiate tolerance and dependence.