Modulation of the hypothermic and hyperglycaemic 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 antagonist may be centrally mediated whereas the blockade of 8-OH-DPAT-induced hyperglycaemia may involve peripheral mechanisms.