Increased GABAB receptor function in mouse frontal cortex after repeated administration of antidepressant drugs or electroconvulsive shocks.
1 Addition of baclofen to a medium containing slices of mouse frontal cortex inhibited the potassium-evoked release of 5-hydroxytryptamine (5-HT) in a concentration-dependent manner. The degree of inhibition was increased in frontal cortex tissue taken from animals treated for 14 days with amitriptyline (10 mg kg-1, twice daily) at all concentrations of baclofen tested (10(-6) M-10(-4) M). 2 Administration of either desipramine, mianserin or zimeldine (10 mg kg-1 daily) for 14 days also approximately doubled the degree of inhibition evoked by addition of baclofen (10(-5) M) to the medium. 3 One day of treatment with the antidepressant drugs did not alter the inhibitory effect of baclofen on K+-evoked 5-HT release. 4 Addition of the antidepressant drugs to the medium had no effect on the K+-evoked release of 5-HT. 5 Repeated administration of electroconvulsive shock (5 seizures spread out over 10 days), like amitriptyline, produced a significant enhancement of the baclofen-induced inhibition of 5-HT release over the range of baclofen concentrations studied. A single electroconvulsive shock had no effect. 6 These data suggest that repeated administration of the antidepressant drugs or electroconvulsive shock increases the function of the gamma-aminobutyric acid (GABA)B receptor in the frontal cortex modulating 5-HT release and are consistent with the finding of increased GABAB receptor number in this region following various antidepressant treatments.
Gray
J A
JA
MRC Unit, Radcliffe Infirmary, Oxford.
Green
A R
AR
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001418:Baclofen / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004597:Electroshock; D005071:Evoked Potentials / Q000187:drug effects; D005479:Flurazepam / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011188:Potassium / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism
D000928:Antidepressive Agents; D011963:Receptors, GABA-A; D012701:Serotonin; D001418:Baclofen; D005479:Flurazepam; D011188:Potassium