Counteraction of the rapid tolerance to 8-OH-DPAT-induced corticosterone secretion in rats by activation of the GABAA receptor-chloride channel complex.

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 gamma-aminobutyric acidA (GABAA) 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 GABAA 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.