Tissue-specific regulation of the peripheral benzodiazepine receptor by antidepressants and lithium.
Peripheral benzodiazepine receptors (PBR) have been identified in peripheral organs as well as in brain glial cells. PBR differ from central benzodiazepine receptors (CBR) in their lack of coupling to the gamma-aminobutyric acid receptors and the chloride ion channels. We investigated the effect of 21 days administration, followed by 7 days withdrawal, of fluvoxamine (10 mg/kg), desipramine (10 mg/kg) and lithium carbonate (25 mg/kg) on PBR and CBR binding characteristics in male Sprague-Dawley rats. All three agents significantly increased PBR density in the testes and adrenals. All tested drugs induced a significant decrease in PBR density in the kidney and liver. After withdrawal, PBR density remained decreased in the liver in all three groups and in the kidneys of the desipramine- and lithium-treated animals. In the cerebral cortex, CBR density increased in response to all three agents, whereas PBR density decreased significantly in response to desipramine and lithium carbonate. Chronic treatment with fluvoxamine, desipramine and lithium carbonate is apparently associated with a modulation in PBR expression in the testes, adrenals, kidneys, liver and brain, and in CBR expression in brain. The relevance of these tissue-selective alterations to the antidepressive and/or anxiolytic effects of these agents, or their adverse effects, still needs to be determined.
Leschiner
S
S
Department of Pharmacology, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Weizman
R
R
Shoukrun
R
R
Veenman
L
L
Gavish
M
M
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D018692:Antimanic Agents / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects; D003891:Desipramine / Q000494:pharmacology*; D016666:Fluvoxamine / Q000494:pharmacology*; D016651:Lithium Carbonate / Q000494:pharmacology*; D008297:Male; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects*
D000928:Antidepressive Agents; D018692:Antimanic Agents; D011963:Receptors, GABA-A; D016651:Lithium Carbonate; D016666:Fluvoxamine; D003891:Desipramine