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Counteraction of the rapid tolerance to 8‐OH‐DPAT‐induced corticosterone secretion in rats by activation of the GABA A receptor‐chloride channel complex
Author(s) -
Kelder Diana,
Ross Svante B.
Publication year - 1993
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.1476-5381.1993.tb13555.x
Subject(s) - muscimol , endocrinology , corticosterone , medicine , bicuculline , picrotoxin , chemistry , gabaa receptor , 8 oh dpat , diazepam , pharmacology , receptor , serotonin , 5 ht receptor , biology , hormone
1 The effect of various classes of compounds on the rapidly developed tolerance to 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin (8‐OH‐DPAT)‐induced corticosterone secretion was examined. 2 Compounds activating the γ‐aminobutyric acid A (GABA A ) receptor‐chloride complex, i.e. muscimol (3 mg kg −1 ), diazepam (5 mg kg −1 ), flunitrazepam (1 mg kg −1 ), sodium pentobarbitone (10–30 mg kg −1 ) and chlormethiazole ethane disulphonate (50 mg kg −1 ) counteracted the development of tolerance when injected before or simultaneously with, but not 15 min after 8‐OH‐DPAT. 3 At these doses the compounds produced an acute increase in serum corticosterone but had, with the exception of muscimol, no effect on the response to the challenge dose of 8‐OH‐DPAT 24 h later. Muscimol significantly decreased the response. 4 The GABA A chloride channel antagonist, picrotoxin (1 mg kg −1 , s.c.), but not bicuculline (1 mg kg −1 , i.p.) potentiated the development of tolerance to 8‐OH‐DPAT‐induced corticosterone secretion. 5 A number of compounds with widely differing pharmacological actions were examined and found to have no effect on the development of tolerance to 8‐OH‐DPAT‐induced corticosterone secretion.