Continuous alpha 2-adrenoceptor blockade by atipamezole decreases neocortical high-voltage spindle activity in rats

The present study investigates the effects of a subchronic continuous infusion of atipamezole, a potent and selective alpha 2-adrenoceptor antagonist, on neocortical high-voltage spindle (HVS) activity in rats. Six days' subcutaneous infusion of atipamezole (0.125 mg/kg per h) with osmotic minipumps decreased HVS activity significantly. The HVS activity-decreasing effect of atipamezole persisted at the same level throughout the infusion. A single subthreshold dose of an alpha 2-adrenoceptor agonist, guanfacine (0.001 mg/kg i.p.), did not affect HVS activity either before or after the continuous atipamezole treatment. The central alpha 2-adrenoceptor blocking effect of atipamezole (0.1 mg/kg per h s.c.) was confirmed to be at the same level after one, three or seven days' infusion, as assessed by measuring the antagonism of detomidine-induced mydriasis in the rat. The serum concentration of atipamezole (0.1 mg/kg per h s.c.) increased slightly from day 3 (37 +/- 11 ng/ml) to day 7 (45 +/- 4 ng/ml). In conclusion, the results of the study suggest that the suppressant effects of atipamezole on neocortical high-voltage spindle activity are preserved during subchronic continuous treatment. In addition, alpha 2-adrenoceptor blockade, as measured in the rat mydriasis model, persists at the same level during subchronic infusion.