Release of endogenous 5-hydroxytryptamine in rat ventral hippocampus evoked by electrical stimulation of the dorsal raphe nucleus as detected by microdialysis: Sensitivity to tetrodotoxin, calcium and calcium antagonists

Sharp, Trevor; Bramwell, S.; Grahame‐Smith, D. G.

doi:10.1016/0306-4522(90)90247-2

Cited by 78 publications

(54 citation statements)

References 30 publications

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“…The inhibition of the 5-HT output produced by TTX in presence of milnacipran was similar to that observed previously for basal 5-HT (Carboni and Di Chiara 1989;Auerbach et al 1989;Sharp et al 1990). The relatively smaller effect of the omission of Ca 2ϩ ions is also consistent with previous observations on basal 5-HT release (Auerbach et al 1989;Sharp et al 1990) and is likely attributable to the fact that endogenous Ca 2ϩ stores in the tissue are sufficient to maintain a substantial degree of neuronal 5-HT release.…”

Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 89%

“…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). The inhibition of the 5-HT output produced by TTX in presence of milnacipran was similar to that observed previously for basal 5-HT (Carboni and Di Chiara 1989;Auerbach et al 1989;Sharp et al 1990). The relatively smaller effect of the omission of Ca 2ϩ ions is also consistent with previous observations on basal 5-HT release (Auerbach et al 1989;Sharp et al 1990) and is likely attributable to the fact that endogenous Ca 2ϩ stores in the tissue are sufficient to maintain a substantial degree of neuronal 5-HT release.…”

Section: Discussionsupporting

confidence: 79%

“…The inhibition of the 5-HT output produced by TTX in presence of milnacipran was similar to that observed previously for basal 5-HT (Carboni and Di Chiara 1989; Auerbach et al. 1989;Sharp et al 1990). The relatively smaller effect of the omission of Ca 2ϩ ions is also consistent with previous observations on basal 5-HT release (Auerbach et al.…”

supporting

confidence: 90%

“…The relatively smaller effect of the omission of Ca 2ϩ ions is also consistent with previous observations on basal 5-HT release (Auerbach et al. 1989;Sharp et al 1990) and is likely attributable to the fact that endogenous Ca 2ϩ stores in the tissue are sufficient to maintain a substantial degree of neuronal 5-HT release.The EC 50 values obtained for milnacipran ‫11ف(‬ mol/l) are comparable to those found for clomipramine (Adell and Artigas 1991) and imipramine (Bel and Artigas 1996) using the same methodology and probe type and size. However, the calculated EC 50 values were close to the lower milnacipran concentration used, which may reduce the accuracy of this measure.…”

supporting

confidence: 89%

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

Bel

Artigas

1999

Neuropsychopharmacology

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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...

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 79%

supporting

confidence: 90%

supporting

confidence: 89%

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

Bel

Artigas

1999

Neuropsychopharmacology

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Serotonin neuronal release from dorsal hippocampus following electrical stimulation of the dorsal and median raph� nuclei in conscious rats

et al. 1998

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We have studied 5-hydroxytryptamine (5-HT) release in the hippocampal formation following electrical stimulation of the dorsal and median raphe ´nuclei in the behaving rat. The primary finding in this study is a decrease in neuronal release of serotonin in the dorsal hippocampal formation following electrical stimulation of either the dorsal or median raphe ´nucleus in conscious rats. At no time did electrical stimulation of either raphe ´nucleus result in behavioral, including vigilance state, changes. The amount of 5-HT released was found to be frequency dependent with higher frequencies (20 Hz) producing larger decreases in release of 5-HT. However, the pattern of release differs between the two raphe ´nuclei. Extracellular levels of 5-HT decrease during stimulation of the dorsal raphe ´, whereas levels decrease only following cessation of stimulation of the median raphe ´nucleus. This may relate to the patterns of innervation of the dorsal hippocampal formation by these two midbrain raphe ´nuclei and also may reflect an inhibition of median raphe ´cell firing during stimulation of the dorsal raphe ´. Electrical stimulation of the dorsal raphe ´in anesthetized animals resulted in an enhanced release of 5-HT. The suppression of 5-HT release in the dorsal hippocampal formation in behaving animals was long-lasting (over 2 h), suggesting that the control mechanisms that regulate 5-HT release operate over a long time-course. This difference in release between non-anesthetized and anesthetized animals may relate to anesthesia blocking long-and/or short-loop serotonin recurrent axonal collaterals negatively feeding back onto 5-HT 1A and 5-HT 1D somatodendritic autoreceptors on raphe ´neurons. Further, the anesthetized animal has diminished monoaminergic ''gating'' influences on the hippocampal formation, whereas the behaving animal is more complex with behavioral (vigilance) states associated with different patterns of gating of information flow through the hippocampal formation.

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Basal and stimulated extracellular serotonin concentration in the brain of rats with altered serotonin uptake

Romero

Jernej

Bel

et al. 1998

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We examined the relationship between the density of serotonergic (5-hydroxytryptamine [5-HT]) uptake sites and extracellular 5-HT concentration in the rat brain using microdialysis with two different models, lesions with 5,7-dihydroxytryptamine (50 microg in the dorsal raphe nucleus (DRN) 15 days before) and sublines of rats genetically selected displaying extreme values of platelet 5-HT uptake. Compared to controls, lesioned rats had a reduced cortical concentration of 5-hydroxyindoles (45%), unchanged basal extracellular 5-HT in the DRN and ventral hippocampus (VHPC), and reduced basal 5-hydroxyindoleacetic acid (5-HIAA) concentrations (46%, DRN; 22%, VHPC). Yet the perfusion of 100 mmol/L KCl or 1 micromol/L citalopram elevated dialysate 5-HT significantly more in the DRN and VHPC of controls. In genetically selected rats, platelet 5-HT content and uptake were highly correlated (r2 = 0.9145). Baseline dialysate 5-HT (VHPC) was not different between high and low 5-HT rats and from normal Wistar rats. However, KCl or citalopram perfusion increased dialysate 5-HT significantly more in high 5-HT than in low 5-HT rats, and the former displayed a greater in vivo tissue 5-HT recovery. Significant but small differences in the same direction were noted in [3H]citalopram binding in several brain areas, as measured autoradiographically. Thus, basal extracellular 5-HT (but not 5-HIAA) concentrations are largely independent on the density of serotonergic innervation and associated changes in uptake sites. However, marked differences emerge during axonal depolarization or reuptake blockade. The significance of these findings for the treatment of mood disorders in patients with neurological disorders is discussed.

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Release of endogenous 5-hydroxytryptamine in rat ventral hippocampus evoked by electrical stimulation of the dorsal raphe nucleus as detected by microdialysis: Sensitivity to tetrodotoxin, calcium and calcium antagonists

Cited by 78 publications

References 30 publications

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

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

Serotonin neuronal release from dorsal hippocampus following electrical stimulation of the dorsal and median raph� nuclei in conscious rats

Basal and stimulated extracellular serotonin concentration in the brain of rats with altered serotonin uptake

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