MODULATION OF THE HYPOTHERMIC AND HYPERGLYCEMIC EFFECTS OF 8-OH-DPAT BY ALPHA-2-ADRENOCEPTOR ANTAGONISTS

1 The effects of pretreatment with two novel and relatively specific alpha-2-adrenoceptor antagonists on the hypothermic and hyperglycaemic responses induced by the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) were investigated in mice. The alpha-2-adrenoceptor antagonists used were, atipamezole, which occupies both central and peripheral receptors, and L 659,066, which poorly penetrates the blood brain barrier. 2 Atipamezole (1 and 3 mg kg-1) alone had no effect on body temperature but significantly attenuated the 8-OH-DPAT-induced hypothermic response. The hyperglycaemic effect of 8-OH-DPAT was also attenuated by pretreatment with atipamezole; however, 3 mg kg-1 atipamezole did cause some hypoglycaemia when administered alone. 3 Pretreatment with L 659,066 (3-30 mg kg-1) failed to alter the hypothermic effects of 8-OH-DPAT. All doses of L 659,066 tested attenuated 8-OH-DPAT-induced hyperglycaemia, but the highest dose (30 mg kg-1) produced hypoglycaemia when administered alone. 4 The results suggest that the attenuation of 8-OH-DPAT-induced hypothermia by alpha-2-adrenoceptor antagonists may be centrally mediated whereas the blockade of 8-OH-DPAT-induced hyperglycaemia may involve peripheral mechanisms.