Tissue-Specific Regulation of the Peripheral Benzodiazepine Receptor by Antidepressants and Lithium

Abstract

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 γ-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.

Enhancing Neurosteroid Synthesis – Relationship to the Pharmacology of Translocator Protein (18 kDa) (TSPO) Ligands and Benzodiazepines

“…Therefore, TSPO protein upregulation does probably not play an outstanding role for the modulation of neurosteroid synthesis by XBD173. Comparable results in terms of TSPO protein expression were obtained for etifoxine and diazepam, thereby pointing out that TSPO upregulation might rather be an unspecific epiphenomenon upon many different stimuli [17,18]. Also for etifoxine we did not find a correlation between TSPO binding affinity and neurosteroid synthesis.…”

A renoprotective role of chitosan against lithium-induced renal toxicity in rats

“…The third group (Lithium-treated): rats were injected intraperitoneally (i.p.) with Li 2 CO 3 solution (25 mg/kg Li 2 CO 3 solution in saline) twice daily for 30 days (Leschiner et al 2000). The fourth group (CS pre-treated): rats were treated with CS orally for 14 days followed be injection with Li 2 CO 3 solution i.p.…”

Translocator Protein (TSPO) Expression in Platelets of Depressed Patients Decreases during Antidepressant Therapy

“…These results from rodent studies challenge our findings of reduced TSPO levels in platelets after antidepressant treatment. However, this may again be related to tissue-specificity, as shown by Leschiner et al [26] or species differences. To clarify the influence of specific compounds, future studies should investigate TSPO expression during the course of the respective pharmacological treatment in a larger sample.…”