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

Article date: May 1993

By: Diana Kelder, Svante B. Ross, in Volume 109, Issue 1, pages 207-212

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.

Compounds activating the γ‐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.

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.

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.

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.

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.

Compounds activating the γ‐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.

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.

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.

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.

DOI: 10.1111/j.1476-5381.1993.tb13555.x

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