Electrophysiologic analysis of antidepressant drug effects on the GABA(A) receptor complex based upon antagonist-induced encephalographic power spectrum changes

To better understand antidepressant drug effects on the GABAA receptor comp lex (the GABAA receptor, chloride ionophore and benzodiazepine receptor), w e investigated how antidepressants influenced power spectrum changes induce d by pentylenetetrazol (PTZ), a chloride ionophore antagonist, in the rat h ippocampal electroencephalogram (EEG). In control recording, PTZ (27.5 mg/k g i.p.) increased EEG power at frequencies under 12 Hn up to five times. Af ter rats were pretreated with imipramine, fluoxetine or trazodone for 7 day s (10 mg/kg i.p., twice a day), PTZ could not increase EEG power to more th an three times the power before injection; this effect was not observed aft er pretreatment for 3 days. These three antidepressants inhibit serotonin u ptake, while two other antidepressants, desipramine and nortriptyline, that inhibit norepinephrine uptake failed to counter the PTZ effect. We conclud ed that antidepressants with serotonergic effects enhanced the function of the GABAA receptor complex. Copyright (C) 2000 S. Karger AG. Basel.