Effect of 5-HT1A Receptor Antagonists on Citalopram-induced Increase in Extracellular Serotonin in the Frontal Cortex, Striatum and Dorsal Hippocampus

Invernizzi, Roberto William; Velasco, Cristina; Bramante, Mario; Longo, Anna; Samanin, R.

doi:10.1016/s0028-3908(97)00060-9

Cited by 92 publications

(64 citation statements)

References 27 publications

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“…It might be argued that such a partial agonist action of (-)-pindolol at 5-HT 1A autoreceptors is inconsistent with its minimal suppressive influence upon FCX levels of 5-HT seen herein and in other studies (Assie and Koek 1996;Hjorth and Sharp 1993;Sharp and Hjorth 1990). However, 1) the firing rate of dorsal raphe nucleus neurones is not invariably reflected in release at the terminal level (Davidson and Stamford 1998); 2) there are regional differences in the effects of 5-HT 1A autoreceptor stimulation upon postsynaptic levels of 5-HT (Invernizzi et al 1997;Kreiss and Lucki 1997;Malagié et al 1996;Romero and Artigas 1997); and 3) antagonist actions at 5-HT 1B terminals (see below) may mask its partial agonist actions at raphe-localized 5-HT 1A receptors (Assie and Koek 1996). In any case, the antagonist actions of (-)-pindolol at 5-HT 1A autoreceptors clearly prevailed in its antagonism of the inhibitory influence of 8-OH-DPAT upon FCX levels of 5-HT seen herein and elsewhere (Sharp and Hjorth 1990) (Figure 2).…”

Section: Discussioncontrasting

confidence: 65%

Modulation of Dialysate Levels of Dopamine, Noradrenaline, and Serotonin (5-HT) in the Frontal Cortex of Freely-Moving Rats by (-)-Pindolol Alone and in Association with 5-HT Reuptake Inhibitors Comparative Roles of β-Adrenergic, 5-HT1A, and 5-HT1B Receptors

Gobert

Millan

1999

Neuropsychopharmacology

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Section: Discussioncontrasting

confidence: 65%

Modulation of Dialysate Levels of Dopamine, Noradrenaline, and Serotonin (5-HT) in the Frontal Cortex of Freely-Moving Rats by (-)-Pindolol Alone and in Association with 5-HT Reuptake Inhibitors Comparative Roles of β-Adrenergic, 5-HT1A, and 5-HT1B Receptors

Gobert

Millan

1999

Neuropsychopharmacology

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“…Several previous microdialysis studies have also reported that (7)-penbutolol enhances the e ects of SSRIs on extracellular 5-HT, an e ect which has been consistently attributed to 5-HT 1A receptor antagonism (Hjorth, 1993;Gundlah et al, 1997;Invernizzi et al, 1997). Interestingly however, in our electrophysiological experiments, we found that (7)-penbutolol appeared to act as an agonist at the somatodendritic 5-HT 1A autoreceptor.…”

Section: Discussionsupporting

confidence: 53%

Effects of (−)‐tertatolol, (−)‐penbutolol and (±)‐pindolol in combination with paroxetine on presynaptic 5‐HT function: anin vivomicrodialysis and electrophysiological study

Gartside

Clifford

Cowen

et al. 1999

British J Pharmacology

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1 The antidepressant e cacy of selective serotonin reuptake inhibitors (SSRIs) might be enhanced by co-administration of 5-HT 1A receptor antagonists. Thus, we have recently shown that the selective 5-HT 1A receptor antagonist, WAY 100635, blocks the inhibitory e ect of an SSRI on 5-HT cell ®ring, and enhances its ability to elevate extracellular 5-HT in the forebrain. Here we determined whether the b-adrenoceptor/5-HT 1A receptor ligands (+)-pindolol, (7)-tertatolol and (7)-penbutolol, interact with paroxetine in a similar manner. 2 Both (7)-tertatolol (2.4 mg kg 71 i.v.) and (7) 3 In electrophysiological studies (7)-tertatolol (2.4 mg kg 71 i.v.) alone had no e ect on 5-HT cell ®ring but blocked the inhibitory e ect of paroxetine. In contrast, (7)-penbutolol (0.1 ± 0.8 mg kg 71 i.v.) itself inhibited 5-HT cell ®ring, and this e ect was reversed by WAY 100635 (0.1 mg kg 71 i.v.). We have recently shown that (+)-pindolol inhibits 5-HT cell ®ring via a WAY 100635-sensitive mechanism. 4 Our data suggest that (7)-tertatolol enhances the e ect of paroxetine on forebrain 5-HT via blockade of 5-HT 1A autoreceptors which mediate paroxetine-induced inhibition of 5-HT cell ®ring. In comparison, the mechanisms by which (7)-penbutolol enhances the e ect of paroxetine on extracellular 5-HT is unclear, since (7)-penbutolol itself appears to have agonist properties at the 5-HT 1A autoreceptor. Indeed, the agonist action of (+)-pindolol at 5-HT 1A autoreceptors probably explains its inability to enhance the e ect of paroxetine on 5-HT in the frontal cortex. 5 Overall, our data suggest that both (7)-tertatolol and (7)-penbutolol are superior to (+)-pindolol in terms of enhancing the e ect of an SSRI on extracellular 5-HT. Both (7)-tertatolol and (7)-penbutolol are worthy of investigation for use as adjuncts to SSRIs in the treatment of major depression.

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“…This suggests that the 5-HT elevation produced by this citalopram concentration was sufficient to activate postsynaptic 5-HT 1A receptors and self-attenuate 5-HT release. In the absence of citalopram, WAY 100635 administration does not increase 5-HT ext in this and other forebrain areas of unanesthetized rats (Invernizzi et al, 1997;Romero and Artigas, 1997;Hervás et al, 2000;Romero et al, unpublished observations).…”

Section: -Ht and Dual Action Antidepressant L Romero Et Almentioning

confidence: 81%

Modulation of Serotonergic Function in Rat Brain by VN2222, a Serotonin Reuptake Inhibitor and 5-HT1A Receptor Agonist

Romero

Celada

Martı́n-Ruiz

et al. 2002

Neuropsychopharmacol

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VN2222(1-(benzo [b]thiophen-3-yl)-3-[4-(2-methoxiphenyl piperazin-1-yl]propan-1-ol) is a potential antidepressant with high affinity for the serotonin transporter and 5-HT 1A receptors. Locally applied, VN2222 enhanced the extracellular 5-hydroxytryptamine (5-HT) concentration (5-HT ext ) in rat striatum to 780% of baseline whereas its systemic administration (1-10 mg/kg s.c.) reduced 5-HT ext . In the presence of citalopram, 8-OH-DPAT or VN2222 applied in medial prefrontal cortex reduced 5-HT ext . Fluoxetine, VN2222, and 8-OH-DPAT suppressed the firing rate of dorsal raphe 5-HT neurons (ED 50 : 790, 14.9, and 0.8 mg/kg i.v., respectively). These effects were antagonized by WAY 100635. Administration of VN2222 for 2 weeks desensitized 5-HT 1A receptors as assessed by microdialysis and single-unit recordings (ED 50 values for 8-OH-DPAT were 0.45 and 2.34 mg/kg i.v. for controls and rats treated with 6 mg/kg day VN2222). These results show that VN2222 is a mixed 5-HT reuptake inhibitor/5-HT 1A agonist that markedly desensitizes 5-HT 1A autoreceptors. These properties suggest that it may be a clinically effective dual action antidepressant drug.

show abstract

Effect of 5-HT1A Receptor Antagonists on Citalopram-induced Increase in Extracellular Serotonin in the Frontal Cortex, Striatum and Dorsal Hippocampus

Cited by 92 publications

References 27 publications

Modulation of Dialysate Levels of Dopamine, Noradrenaline, and Serotonin (5-HT) in the Frontal Cortex of Freely-Moving Rats by (-)-Pindolol Alone and in Association with 5-HT Reuptake Inhibitors Comparative Roles of β-Adrenergic, 5-HT1A, and 5-HT1B Receptors

Modulation of Dialysate Levels of Dopamine, Noradrenaline, and Serotonin (5-HT) in the Frontal Cortex of Freely-Moving Rats by (-)-Pindolol Alone and in Association with 5-HT Reuptake Inhibitors Comparative Roles of β-Adrenergic, 5-HT1A, and 5-HT1B Receptors

Effects of (−)‐tertatolol, (−)‐penbutolol and (±)‐pindolol in combination with paroxetine on presynaptic 5‐HT function: anin vivomicrodialysis and electrophysiological study

Modulation of Serotonergic Function in Rat Brain by VN2222, a Serotonin Reuptake Inhibitor and 5-HT1A Receptor Agonist

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