[A study of the effects of antidepressants on the GABAA receptor and its complex based on the drug actions on the power-spectral changes of rat hippocampal EEG induced by GABA antagonists and inverse agonists].
To analyze the effects of antidepressants on the GABAA receptor, we investigated how the chronic administration of antidepressants (10 mg/kg twice a day for three or seven days, ip) influenced the power-spectral changes induced by pentylenetetrazol (PTZ; a GABA antagonist; 27.5 mg/kg) or beta-carboline-3-carboxylic-acid-methylester (beta-CCM; an inverse agonist; 1 mg/kg) on rat hippocampal EEGs. PTZ and beta-CCM are known to inhibit the chloride ionophore and benzodiazepine receptor (GABAA receptor complex), respectively. After the ip injection of both compounds, the EEG power under 12 Hz increased to about five times that before injection. Between the rats that did not receive any antidepressants and all those injected with the drugs for 3 days or treated with desipramine (DMI) for 7 days, there were no apparent changes in the effect of PTZ or beta-CCM. However, in the rats treated with imipramine, fluoxetine or trazodone for 7 days, the increase in power after the injection of PTZ or beta-CCM was apparently suppressed. In these rats, the power values were less than three times those before the dosing of PTZ or beta-CCM. DMI is known to inhibit the re-uptake of norepinephrine (NE), while the other three antidepressants inhibit that of serotonin (5-HT). Trazodone is also reported to block the 5-HT2 sites. These observations might indicate that the chronic administration of antidepressants prompted the function of the GABAA receptor complex. Moreover, it is also suggested that, to that action, the effect of antidepressants on the 5-HT system or interaction between the 5-HT system and GABA receptors might play some role.
Matsubara
M
M
Department of Neuropsychiatry, Aichi Medical College, Japan.
Suzuki
S
S
Miura
K
K
Terashima
M
M
Hatsuda
S
S
Sugita
S
S
Murakami
H
H
Nakazawa
K
K
Ohara
M
M
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002243:Carbolines / Q000494:pharmacology*; D003864:Depression, Chemical; D003891:Desipramine / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects*; D005473:Fluoxetine / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology*; D006624:Hippocampus / Q000502:physiology; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010433:Pentylenetetrazole / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D014196:Trazodone / Q000494:pharmacology
D000928:Antidepressive Agents; D002243:Carbolines; D018756:GABA Antagonists; D011963:Receptors, GABA-A; D005473:Fluoxetine; D012701:Serotonin; C036150:beta-carboline-3-carboxylic acid methyl ester; D007099:Imipramine; D003891:Desipramine; D010433:Pentylenetetrazole; D009638:Norepinephrine; D014196:Trazodone