Citalopram's ability to increase the extracellular concentrations of serotonin in the dorsal raphe prevents the drug's effect in the frontal cortex

Section: Strain-related Differences In the Effects Of Citalopram On Cmentioning

confidence: 99%

Serotonin Reuptake Inhibition by Citalopram in Rat Strains Differing for Their Emotionality

Pollier

Sarre

Aguerre

et al. 2000

Section: Discussionmentioning

confidence: 86%

“…The 5-HT elevations in frontal cortex and raphe nuclei were comparable. This regional selectivity is different from that of agents that selectively block 5-HT reuptake, which enhances extracellular 5-HT more in the raphe nuclei than in frontal cortex (Adell and Artigas 1991; Bel and Artigas 1992;Invernizzi et al 1992;Malagié et al 1995;Hervás and Artigas 1998).Milnacipran markedly elevated the 5-HT output in rat brain when administered by reverse dialysis (7-and 10-fold in frontal cortex and midbrain, respectively). The antagonism of this effect by the omission of Ca 2ϩ ions and the addition of TTX indicates that milnacipran elevated the 5-HT output by blockade of the reuptake of the 5-HT released by an impulse-dependent mechanism and not by a fenfluramine-like releasing action, because the latter is insensitive to the blockade of nerve transmission (Carboni and Di Chiara 1989).…”

mentioning

confidence: 81%

“…The baseline 5-HT output was unaffected by 2-week treatments with milnacipran (30 and 60 mg/kg и day). The distinct regional profile and the lack of enhancement of its effects by WAY-100635 and prolonged treatment suggest that milnacipran does not exert itsThe administration of selective 5-HT reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), and clomipramine markedly increases the extracellular concentration of 5-HT in the raphe nuclei of the midbrain (Adell and Artigas 1991; Bel and Artigas 1992;Invernizzi et al 1992;Celada and Artigas 1993;Gartside et al 1995;Malagié et al 1995). In all instances, these elevations are superior to those produced in frontal cortex or, when examined, in hippocampus.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Modulation of the Extracellular 5-Hydroxytryptamine Brain Concentrations by the Serotonin and Noradrenaline Reuptake Inhibitor, Milnacipran Microdialysis Studies in Rats

Bel

Artigas

1999

We examined the effects of the administration of milnacipran, a dual inhibitor of serotonin (5-hydroxytryptamine, 5-HT) and noradrenaline uptake on the 5-HT output in rat brain. Local milnacipran administration increased the 5-HT output in frontal cortex and the midbrain raphe nuclei 7-and 10-fold by a Ca 2 ϩ -and tetrodotoxin-dependent mechanism. However, the subcutaneous administration of milnacipran (1-60 mg/kg SC) elevated the 5-HT output much less in these areas (200-230% of baseline at 60 mg/kg). In hypothalamus, 10 mg/kg SC raised 5-HT levels to 170%. The 5-HT 1A antagonist WAY-100635 caused a small potentiation of the effects of milnacipran. The baseline 5-HT output was unaffected by 2-week treatments with milnacipran (30 and 60 mg/kg и day). The distinct regional profile and the lack of enhancement of its effects by WAY-100635 and prolonged treatment suggest that milnacipran does not exert itsThe administration of selective 5-HT reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), and clomipramine markedly increases the extracellular concentration of 5-HT in the raphe nuclei of the midbrain (Adell and Artigas 1991; Bel and Artigas 1992;Invernizzi et al. 1992;Celada and Artigas 1993;Gartside et al. 1995;Malagié et al. 1995). In all instances, these elevations are superior to those produced in frontal cortex or, when examined, in hippocampus. The excess 5-HT in the extracellular space of the midbrain raphe activates 5-HT 1A autoreceptors in the soma and dendrites of serotonergic neurones and reduces the neuronal activity and release of 5-HT by nerve terminals in forebrain (see for review).Selective serotonin (5-hydroxytryptamine, 5-HT) and noradrenaline reuptake inhibitors (SNRIs) are a new class of antidepressant drugs. These agents inhibit in vitro the neuronal uptake of 5-HT and noradrenaline without exhibiting significant activity at the dopamine transporter or aminergic receptors (see Artigas 1995; Briley 1998 for review). Consequently, they are devoid of the unwanted side effects of classic antidepressant Received January 17, 1999; revised May 21, 1999; accepted June 18, 1999. 746 N. Bel and F. Artigas N EUROPSYCHOPHARMACOLOGY 1999 -VOL . 21 , NO . 6 drugs, mainly derived from their affinity for ␣ -adrenergic, cholinergic, and histamine receptors (Richelson 1978;Richelson and Nelson 1984). Milnacipran is one such drug that blocks in vitro and in vivo the reuptake of 5-HT and noradrenaline, although it displays a slightly higher affinity for the latter (Moret et al. 1985;Stenger et al. 1987).Despite the potential advantages of SNRIs, the information on their in vivo effects on serotonergic transmission is scarce (e.g., Engleman et al. 1995;. In particular, a comparison of their effects in the somatodendritic region in the raphe nuclei and in forebrain has not been performed. Data obtained with the microdialysis technique suggest that the dual blockade of the 5-HT and noradrenaline transporters elevates the extracellular 5-HT concentration in rat brain, with a regional profile d...

“…Neurochemical studies have shown that antidepressant drugs that inhibit the serotonin transporter (e.g., SSRIs and certain tricyclics) preferentially increase the concentration of extracellular serotonin in the midbrain raphe, presumably because this region has the highest density of serotonin uptake sites in the brain (Adell and Artigas 1991;Invernizzi et al 1992;Artigas 1993;Hervás and Artigas 1998). The increase in raphe serotonin leads to an inhibition of serotonergic neuronal activity through enhanced activation of somatodendritic 5-HT 1A autoreceptors (Blier and de Montigny 1994).…”

Section: Discussionmentioning

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...