Tissue-specific regulation of the peripheral benzodiazepine receptor by antidepressants and lithium

Peripheral benzodiazepine receptors (PBR) have been identified in periphera l organs as well as in brain glial cells. PER differ from central benzodiaz epine receptors (CBR) in their lack of coupling to the gamma-aminobutyric a cid receptors and the chloride ion channels. We investigated the effect of 21 days administration, followed by 7 days withdrawal, of fluvoxamine (10 m g/kg), desipramine (10 mg/kg) and lithium carbonate (25 mg/kg) on PER and C BR binding characteristics in male Sprague-Dawley rats. All three agents si gnificantly increased PER density in the testes and adrenals. All tested dr ugs induced a significant decrease in PER density in the kidney and liver. After withdrawal, PER 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 agen ts, whereas PER 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 PER express ion in the testes, adrenals, kidneys, liver and brain, and in CBR expressio n in brain. The relevance of these tissue-selective alterations to the anti depressive and/or anxiolytic effects of these agents, or their adverse effe cts, still needs to be determined. Copyright (C) 2000 S. Karger AG, Basel.