A microdialysis study of the <i>in vivo</i> release of 5‐HT in the median raphe nucleus of the rat

Adell, Albert; Artigas, Francesc

doi:10.1038/sj.bjp.0702206

Cited by 62 publications

(61 citation statements)

References 54 publications

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“…The concentration of 5-HT in dialysate samples was determined by an HPLC system consisting of a Waters 717plus autosampler (Waters Cromatografia, Cerdanyola, Spain), a Hewlett-Packard series 1050 pump (Agilent Technologies, Las Rozas, Spain), a 3-mM octadecylsilica (ODS) column (7.5 cm Â 0.46 cm; Beckman, San Ramon, CA), and an amperometric detector Hewlett-Packard 1049 (Agilent Technologies) set at an oxidation potential of 0.6 V. The mobile phase consisted of 0.15 M NaH 2 PO 4 , 1.8 mM octyl sodium sulfate, 0.2 mM EDTA (pH 2.8, adjusted with phosphoric acid), and 30% methanol and was pumped at 0.7 ml/min (Adell and Artigas, 1998). For the determination of glutamate, another HPLC system was used, which consisted of a Waters 717plus autosampler, a Waters 600 quaternary gradient pump, and a Nucleosil 5-mM ODS column (10 cm Â 0.4 cm; Teknokroma, Spain).…”

Section: Biochemical Determinationsmentioning

confidence: 99%

Clozapine and Haloperidol Differently Suppress the MK-801-Increased Glutamatergic and Serotonergic Transmission in the Medial Prefrontal Cortex of the Rat

López-Gil

Babot

Amargós-Bosch

et al. 2007

Neuropsychopharmacol

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170

162

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The administration of noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists such as phencyclidine and ketamine has been shown to increase the extracellular concentration of glutamate and serotonin (5-HT) in the medial prefrontal cortex (mPFC). In the present work, we used in vivo microdialysis to examine the effects of the more potent noncompetitive NMDA receptor antagonist, MK-801, on the efflux of glutamate and 5-HT in the mPFC, and whether the MK-801-induced changes in the cortical efflux of both transmitters could be blocked by clozapine and haloperidol given systemically or intra-mPFC. The systemic, but not the local administration of MK-801, induced an increased efflux of 5-HT and glutamate, which suggests that the NMDA receptors responsible for these effects are located outside the mPFC, possibly in GABAergic neurons that tonically inhibit glutamatergic inputs to the mPFC. The MK-801-induced increases of extracellular glutamate and 5-HT were dependent on nerve impulse and the activation of mPFC AMPA/ kainate receptors as they were blocked by tetrodotoxin and NBQX, respectively. Clozapine and haloperidol blocked the MK-801-induced increase in glutamate, whereas only clozapine was able to block the increased efflux of 5-HT. The local effects of clozapine and haloperidol paralleled those observed after systemic administration, which emphasizes the relevance of the mPFC as a site of action of these antipsychotic drugs in offsetting the neurochemical effects of MK-801. The ability of clozapine to block excessive cortical 5-HT efflux elicited by MK-801 might be related to the superior efficacy of this drug in treating negative/cognitive symptoms of schizophrenia.

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Section: Biochemical Determinationsmentioning

confidence: 99%

Clozapine and Haloperidol Differently Suppress the MK-801-Increased Glutamatergic and Serotonergic Transmission in the Medial Prefrontal Cortex of the Rat

López-Gil

Babot

Amargós-Bosch

et al. 2007

Neuropsychopharmacol

Self Cite

170

162

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“…An updated description of the microdialysis procedures has been published (Adell and Artigas 1998). Rats were anesthetized with pentobarbital (60 mg/kg i.p.)…”

Section: Surgery and Microdialysis Proceduresmentioning

confidence: 99%

“…5-HT was analyzed by a modification of a highperformance liquid chromatography method previously described in an updated form (Adell and Artigas, 1998). 5-HT was separated on a 3 mm ODS 2 column (7.5 cm Â 0.46 cm; Beckman, San Ramon, CA) and detected amperometrically with a Hewlett Packard 1049 detector set at the potential of þ 0.6 V. Retention time was 3.5-4 min.…”

Section: Surgery and Microdialysis Proceduresmentioning

confidence: 99%

The Selective 5-HT2A Receptor Antagonist M100907 Enhances Antidepressant-Like Behavioral Effects of the SSRI Fluoxetine

Marek

Martı́n-Ruiz

Abo

et al. 2005

Neuropsychopharmacol

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112

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The addition of low doses of atypical antipsychotic drugs, which saturate 5-HT 2A receptors, enhances the therapeutic effect of selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) in patients with major depression as well as treatment-refractory obsessive-compulsive disorder. The purpose of the present studies was to test the effects of combined treatment with a low dose of a highly selective 5-HT 2A receptor antagonist (M100907; formerly MDL 100,907) and low doses of a SSRI using a behavioral screen in rodents (the differential-reinforcement-of low rate 72-s schedule of reinforcement; DRL 72-s) which previously has been shown to be sensitive both to 5-HT 2 antagonists and SSRIs. M100907 has a B100-fold or greater selectivity at 5-HT 2A receptors vs other 5-HT receptor subtypes, and would not be expected to appreciably occupy non-5-HT 2A receptors at doses below 100 mg/kg. M100907 increased the reinforcement rate, decreased the response rate, and shifted the inter-response time distributions to the right in a pattern characteristic of antidepressant drugs. In addition, a positive synergistic interaction occurred when testing low doses of the 5-HT 2A receptor antagonist (6.25-12.5 mg/kg) with clinically relevant doses of the SSRI fluoxetine (2.5-5 mg/kg), which both exerted minimal antidepressant-like effects by themselves. In vivo microdialysis study revealed that a low dose of M100907 (12.5 mg/kg) did not elevate extracellular 5-HT levels in the prefrontal cortex over those observed with fluoxetine alone (5 mg/kg). These results will be discussed in the context that the combined blockade of 5-HT 2A receptors and serotonin transporters (SERT) may result in greater efficacy in treating neuropsychiatric syndromes than blocking either site alone.

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“…L358/1 18/12/1986). A detailed description of the microdialysis procedures can be found in Adell and Artigas (1998). Briefly, anesthetized rats (pentobarbital, 60 mg/kg, i.p.)…”

Section: Microdialysis Proceduresmentioning

confidence: 99%

Desensitization of 5-HT1A Autoreceptors by a Low Chronic Fluoxetine Dose Effect of the Concurrent Administration of WAY-100635

Hervás

2001

Neuropsychopharmacology

100

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Using microdialysis, receptor autoradiography and in situ hybridization, we examined the effects of fluoxetine alone or with WAY-100635 on: (a) extracellular 5-HT in frontal cortex; and (b) density and sensitivity of 5-HT 1A autoreceptors in rat brain. WAY-100635 (0.3 mg/kg, s.c.) doubled the increase in extracellular 5-HT produced by fluoxetine (3 mg/kg, i.p.) (SSRI) Selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors (SSRIs) are extensively used in the treatment of major depression. The increase in forebrain extracellular 5-HT elicited by SSRIs is limited by a negative feed-back involving raphe autoreceptors . The prevention of this inhibitory mechanism with 5-HT 1A receptor antagonists augments the neurochemical and behavioral effects of SSRIs (Gartside et al. 1995;Artigas et al. 1996;Hashimoto et al. 1997;Mitchell and Redfern 1997;Grignaschi et al. 1998;Trillat et al. 1998). At the clinical level, the ␤ -adrenoceptor/ 5-HT 1A receptor antagonist pindolol accelerates the antidepressant effects of SSRIs in open-label and placebocontrolled trials Blier and Bergeron 1995;Pérez et al. 1997;Zanardi et al. 1997Zanardi et al. , 1998Bordet et al. 1998). However, its effectiveness to potentiate antidepressant response in chronically ill or treatmentresistant patients is still controversial (Maes et al. 1996(Maes et al. , 1999Berman et al. 1997;Moreno et al. 1997;Pérez et al. 1999). Based on this rationale, selective 5-HT 1A receptor antagonists (for use with SSRIs; add-on strategy) and dual action compounds (5-HT reuptake inhibitor ϩ 5-HT 1A antagonist) are being developed for use in the treatment of major depression. The prolonged administration of SSRIs has been reported to desensitize raphe 5-HT 1A autoreceptors, as assessed by single unit recordings and brain microdialysis (Blier and de Montigny 1994;Invernizzi et al. 1994;Arborelius et al. 1995;Le Poul et al. 1995). This reduces the efficacy of the above negative feedback and increases extracellular 5-HT (Bel and Artigas 1993;Invernizzi et al. 1994;Rutter et al. 1994;Arborelius et al. 1996). Other studies, however, have failed to observe such effects even using large doses of SSRIs (Hjorth and Auerbach 1994a;Bosker et al. 1995;Invernizzi et al. 1995).To our knowledge, there are no published reports on the effects of prolonged treatments with combinations of SSRIs and 5-HT 1A receptor antagonists on these experimental paradigms, except in abstract form (Dawson et al. 1998). As with pindolol, future selective 5-HT 1A receptor antagonists would be administered for a limited period of time. Should prolonged blockade of 5-HT 1A receptor result in receptor sensitization, the withdrawal of the antagonist would increase the efficacy of the above negative feed-back and reduce the ability of the SSRI to increase extracellular 5-HT, thus increasing the possibility of a clinical relapse. Since this is crucial for the success of this therapeutic strategy, we examined the effects of two-week treatments with fluoxetine, WAY-100635 and their combination...

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A microdialysis study of the in vivo release of 5‐HT in the median raphe nucleus of the rat

Cited by 62 publications

References 54 publications

Clozapine and Haloperidol Differently Suppress the MK-801-Increased Glutamatergic and Serotonergic Transmission in the Medial Prefrontal Cortex of the Rat

Clozapine and Haloperidol Differently Suppress the MK-801-Increased Glutamatergic and Serotonergic Transmission in the Medial Prefrontal Cortex of the Rat

The Selective 5-HT2A Receptor Antagonist M100907 Enhances Antidepressant-Like Behavioral Effects of the SSRI Fluoxetine

Desensitization of 5-HT1A Autoreceptors by a Low Chronic Fluoxetine Dose Effect of the Concurrent Administration of WAY-100635

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