Extracts of St. John's wort and various constituents affect β-adrenergic binding in rat frontal cortex

The present study was designed to get further insight into the mode of antidepressant action of extracts prepared from St. John's wort (SJW) and relevant active constituents. Down-regulation of central β-adrenergic receptors (β-AR's) has been widely considered a common biochemical marker of antidepressant efficacy. Although previous studies have reported a β-AR down-regulation for SJW extracts, in vivo studies that compare the effects of SJW extracts with those of relevant active constituents on β-AR density have not been done yet. We used quantitative radioligand receptor-binding-studies to examine in rats the effects of short-term (2 wks) and long-term (8 wks) administration of different SJW extracts and constituents on β-AR binding in rat frontal cortex. The effects were compared to those of the standard antidepressants imipramine and fluoxetine. [ 125I]CYP binding to β-AR was found to be decreased after short as well as after long-term treatment with imipramine (36%, 40%). Short-term treatment with fluoxetine decreased the number of β-adrenergic receptors (17%) while long-term treatment with fluoxetine elicited an increase (14%) in β-AR-binding. This effect was comparable to that of the lipophilic CO 2 extract which decreased β-AR-binding (13%) after two weeks and slightly increased the number of β-AR's after 8 weeks (9%). Short-term treatment with the methanolic SJW extract decreased β-AR-binding (14%), no effects for this extract were observed after 8 weeks. Treatment with hypericin led to a significant down-regulation (13%) of β-AR's in the frontal cortex after 8-weeks, but not after 2 weeks, while hyperforin (used as trimethoxybenzoate, TMB), and hyperoside were ineffective in both treatment paradigms. Compared to the SJW extracts and single compounds the effect of imipramine on β-AR-binding was more pronounced in both treatment paradigms.