Modulatory effect of antidepressants on peripheral-type benzodiazepine receptors.
The effect of 21 days of imipramine hydrochloride (10 mg/kg) and phenelzine sulfate (10 mg/kg) administration followed by a 7-day period of withdrawal on peripheral-type benzodiazepine receptors was studied in male Sprague-Dawley rats. Both imipramine and phenelzine down-regulated adrenal peripheral-type benzodiazepine receptors (-18% P < 0.05; and -32%, P < 0.01, respectively) and up-regulated hepatic peripheral-type benzodiazepine receptors (+27%, P < 0.05; and +76%, P < 0.0001, respectively), while no alteration was observed in the kidney. Adrenal peripheral-type benzodiazepine receptors decreased further (-30% versus controls) after withdrawal from imipramine, while full restoration to normal values occurred following phenelzine withdrawal. [3H]PK 11195 binding to the liver did not differ significantly from the control values after withdrawal from either drug. The observed changes can be explained as adaptive responses to antidepressant-induced hormonal and cellular alterations.
Weizman
R
R
Tel Aviv Community Mental Health Center, Tel Aviv University, Israel.
Burgin
R
R
Gavish
M
M
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D007099:Imipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000493:pharmacokinetics; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity; D017933:Peripheral Nervous System / Q000187:drug effects*; D010624:Phenelzine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
D000928:Antidepressive Agents; D007546:Isoquinolines; D011963:Receptors, GABA-A; D010624:Phenelzine; D007099:Imipramine; C037850:PK 11195