Inhibition of 5-HT cell firing in the DRN by non-selective 5-HT reuptake inhibitors: studies on the role of 5-HT 1A autoreceptors and noradrenergic mechanisms

151

Section: Discussionmentioning

confidence: 96%

mentioning

confidence: 98%

Differential Regulation of 5-HT1A Receptor-G Protein Interactions in Brain Following Chronic Antidepressant Administration

Hensler

2002

151

“…In addition, although St. John's wort has been shown to inhibit the uptake of norepinephrine and dopamine in vitro, it is unlikely that such a blockade would interfere with the ability of serotonin reuptake inhibitors to suppress neuronal activity in vivo. This is supported in part by the fact that dual serotonin/norepinephrine reuptake inhibitors, such as duloxetine and venlafaxine, potently inhibit the firing rate of serotonergic neurons in both the anesthetized and freely moving animal (Gartside et al 1997;Béïque et al 1999;Bjorvatn et al 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Agents which increase the synaptic availability of serotonin in the brain (e.g., serotonin precursors, releasers, uptake blockers, and MAO inhibitors) produce a compensatory decrease in neuronal activity, by activating somatodendritic 5-HT 1A autoreceptors on serotonergic neurons located within the midbrain raphe (Aghajanian and Wang 1978;Aghajanian and VanderMaelen 1986;Gartside et al 1997). This region may be a selective target for serotonergic antidepressant drugs (Artigas 1993).…”

Section: -Hydroxytryptamine (Serotonin); Electrophysiologymentioning

confidence: 99%

Effects of Standardized Extracts of St. John's Wort on the Single-Unit Activity of Serotonergic Dorsal Raphe Neurons in Awake Cats Comparisons with Fluoxetine and Sertraline

Fornal

Metzler

Mirescu

et al. 2001

St. John's wort, p.o.) and i.v.). Both preparations were found to have no effect on neuronal activity. This contrasts sharply with the action of fluoxetine and sertraline (2 mg/kg, p.o.) 8-hydroxy-2-(di-n-propylamino)tetralin (10 g/kg, i.v.). Overall, these -hydroxytryptamine (serotonin); ElectrophysiologyThe medicinal plant Hypericum perforatum L., commonly known as St. John's wort, appears to be an effective antidepressant with few side effects (Hippius 1998;Wheatley 1998;Vitiello 1999). In Germany, where extracts of the plant are licensed as a medication, St. John's wort or hypericum is used more extensively than et al. 1996). Since the publication of that influential report, several other systematic reviews (and one metaanalysis) have appeared which further support the antidepressant efficacy of hypericum (Josey and Tackett 1999;Kim et al. 1999;Stevinson and Ernst 1999;Gaster and Holroyd 2000). Furthermore, in comparison with other antidepressants, St. John's wort is well tolerated and has a low side effect profile (Linde et al. 1996;Ernst et al. 1998 Despite its widespread use, the active constituents and mechanism of antidepressant action of St. John's wort remain largely unknown (Bennett et al. 1998;Nathan 1999). A number of studies have shown that crude hypericum preparations and some of the constituents can inhibit monoamine oxidase (MAO) activity in vitro (Demisch et al. 1989;Thiede and Walper 1994;Cott 1997;. However, the clinical relevance of this pharmacological effect is questionable, since it occurs only at high concentrations and has not been observed in vivo (Bladt and Wagner 1994;Yu 2000). More recent studies have focused on the capacity of St. John's wort to inhibit the uptake of brain monoamines, particularly serotonin Neary and Bu 1999). Perovic and Müller (1995) were the first to report that a crude hypericum extract inhibited the uptake of serotonin in rat cortical synaptosomes at relatively low concentrations and conclude that the antidepressant activity of St. John's wort is due to this action. Hypericum has also been shown to inhibit the synaptosomal uptake of dopamine and norepinephrine, at concentrations similar to those found to inhibit the uptake of serotonin . In subsequent studies, the chemical substance hyperforin was identified as one of the major uptake-inhibiting components of St. John's wort Chatterjee et al. 1998;Singer et al. 1999). The content of this substance has recently been associated with the clinical antidepressant action of St. John's wort (Laakmann et al. 1998), suggesting that hyperforin is at least partially responsible for the antidepressant properties of the herb. Other evidence suggest that hypericum extracts may enhance the release of serotonin from presynaptic stores (Gobbi et al. 1999). Neurochemical studies have shown that St. John's wort increases serotonin metabolism and/or turnover in various brain regions (Calapai et al. 1999;Yu 2000). Finally, it has been hypothesized that the clinical efficacy of St. John's wort may result from a combinati...

“…Based on their binding affinities, ziprasidone, clozapine, and olanzapine each may act through ␣ 1 receptors (Table 1), antagonists of which are known to inhibit serotonin neuronal firing (Baraban and Aghajanian 1980). Desipramine (DMI) has recently been shown to reverse the inhibitory effect of ␣ 1 antagonists on unit activity (Gartside et al 1997); earlier work had demonstrated similar antagonism with l-amphetamine (Gallager and Aghajanian 1976a) or cirazoline, an ␣ 1 agonist (Lejeune et al 1994). In the present study, DMI (5 mg/kg, I.V.)…”

Section: Sensitivity Of Drug-induced Neuronal Inhibition To Way-1006mentioning

confidence: 99%

Comparison of the Novel Antipsychotic Ziprasidone with Clozapine and Olanzapine Inhibition of Dorsal Raphe Cell Firing and the Role of 5-HT1A Receptor Activation

Sprouse

Reynolds

Braselton

et al. 1999