Spinal potentiation and supraspinal additivity in the antinociceptive interaction between systemically administered alpha 2-adrenoceptor agonist and cocaine in the rat.

We studied the antinociceptive interaction of systemically administered medetomidine, a selective alpha 2-adrenoceptor agonist, with cocaine in the tailflick and hotplate tests in rats. In intact rats, both medetomidine alone (25-300 micrograms/kg subcutaneously [SC]) and cocaine alone (10-30 mg/kg intraperitoneally [IP]) produced a dose-dependent antinociception in the supraspinally mediated hotplate test, and their combination (medetomidine 25 micrograms/kg+cocaine 10-20 mg/kg) produced an additive antinociceptive effect. In the spinally mediated tailflick test, only medetomidine alone produced a significant antinociceptive effect both in intact and spinal rats, whereas cocaine alone produced a marginally significant antinociceptive effect in the tailflick test only at the highest dose used (30 mg/kg) and only in intact rats. The combination of medetomidine (25 micrograms/kg SC) with cocaine (10-20 mg/kg IP) produced potentiation of antinociception in the tailflick test both in intact and spinal rats. The results indicate that at the supraspinal level there is an additive antinociceptive interaction between cocaine and medetomidine, whereas at the spinal level cocaine potentiates the medetomidine-induced antinociception independent of supraspinal mechanisms. The results further support previous evidence indicating that antinociception produced by a systemically administered alpha 2-adrenergic drug alone is mainly due to spinal mechanisms, whereas that by systemically administered cocaine alone is mainly due to supraspinal mechanisms.