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.
Kelder
D
D
Department of Neuropharmacology, Södertälje, Sweden.
Ross
S B
SB
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D018118:Chloride Channels; D002719:Chlormethiazole / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood / Q000378:metabolism*; D004361:Drug Tolerance; D007473:Ion Channels / Q000187:drug effects*; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects*; D009118:Muscimol / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects*
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D001569:Benzodiazepines; D001640:Bicuculline; D018118:Chloride Channels; D002719:Chlormethiazole; D003345:Corticosterone; D007473:Ion Channels; D008565:Membrane Proteins; D009118:Muscimol; D010424:Pentobarbital; D010852:Picrotoxin; D011963:Receptors, GABA-A