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Modulation of the hypothermic and hyperglycaemic effects of 8‐OH‐DPAT by α 2 ‐adrenoceptor antagonists
Author(s) -
Durcan Michael J.,
Wozniak Krystyna M.,
Linnoila Markku
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12157.x
Subject(s) - 8 oh dpat , modulation (music) , endocrinology , chemistry , medicine , pharmacology , receptor , 5 ht receptor , serotonin , physics , acoustics
1 The effects of pretreatment with two novel and relatively specific α 2 ‐adrenoceptor antagonists on the hypothermic and hyperglycaemic responses induced by the 5‐HT 1A receptor agonist 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin (8‐OH‐DPAT) were investigated in mice. The α 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 α 2 ‐adrenoceptor antagonists may be centrally mediated whereas the blockade of 8‐OH‐DPAT‐induced hyperglycaemia may involve peripheral mechanisms.