Involvement of dopamine D2 receptors in apomorphine-induced facilitation of forebrain serotonin output

Mendlin, Anna; Martín, Francisco Javier Escalada San; Jacobs, Barry L.

doi:10.1016/s0014-2999(98)00321-5

Cited by 26 publications

(14 citation statements)

References 32 publications

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“…Compared with desvenlafaxine, the intravenous administration of LPM570065 increased extracellular DA levels through the inhibition of DA reuptake. Previous studies have reported that DA might activate the serotonergic system through the activation of postsynaptic D 2 -like receptors [51], [52] and the systemic administration of apomorphine elicits increased serotonergic firing rates and increased 5-HT levels [19], [53]. Administration of a D 2 receptor antagonist (raclopride) attenuated the LPM570065-induced increase in extracellular 5-HT levels within the first 120 min after intravenous administration of LPM570065, and that the reduction in 5-HT levels by raclopride+LPM570065 (i.v.)…”

Section: Discussionmentioning

confidence: 99%

The Effects of LPM570065, a Novel Triple Reuptake Inhibitor, on Extracellular Serotonin, Dopamine and Norepinephrine Levels in Rats

Renyu

Shi

et al. 2014

PLoS ONE

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Triple reuptake inhibitors (TRIs) are currently being developed as a new class of promising antidepressants that block serotonin (5-HT), dopamine (DA) and norepinephrine (NE) transporters, thereby increasing extracellular monoamine concentrations. The purpose of this study was to investigate the effects of LPM570065, a novel TRI and a desvenlafaxine prodrug, on extracellular 5-HT, DA and NE levels in the rat striatum after acute and chronic administration relative to desvenlafaxine, using High Performance Liquid Chromatography (HPLC) and microdialysis. Acute administration was performed by providing rodents with oral solutions (0.06 mmol·kg−1 p.o.), oral suspensions (0.06 mmol·kg−1 p.o.) and intravenous solutions (0.04 mmol·kg−1 i.v.) of LPM570065 and desvenlafaxine. Oral suspensions (0.06 mmol·kg−1·day−1) of the two drugs were also administered for a 14-day chronic period. HPLC analysis revealed that LPM570065 rapidly penetrated the rat striatum, converted into desvenlafaxine and exhibited larger total exposure compared with the administration of desvenlafaxine. Microdialysis revealed that acute and chronic administration of oral suspension of LPM570065 increased the 5-HT, DA and NE levels more than the relative administration of desvenlafaxine. Unlike desvenlafaxine, acute administration of an intravenous LPM570065 solution did not induce the undesirable 90% decrease in extracellular 5-HT levels. In contrast to the fully dose-dependent elevation of 5-HT induced by desvenlafaxine, the acute administration of LPM570065 showed a capped increase in extracellular 5-HT levels when combined with WAY-100635. Additionally, forced swim test demonstrated that acute and chronic administration of LPM570065 reduced the immobility time more than the relative administration of desvenlafaxine. These data suggest that LPM570065 may have greater efficacy and/or a more rapid onset of antidepressant action than desvenlafaxine and also counterbalance the harmful effects of desvenlafaxine on 5-HT neurotransmission related to 5-HT1A autoreceptors. Thus, this new class of drugs, TRIs has the potential to provide a new therapeutic mechanism for treating depression.

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Section: Discussionmentioning

confidence: 99%

The Effects of LPM570065, a Novel Triple Reuptake Inhibitor, on Extracellular Serotonin, Dopamine and Norepinephrine Levels in Rats

Renyu

Shi

et al. 2014

PLoS ONE

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“…A number of functional studies indicate that DA exerts a facilitatory effect on central 5‐HT neurotransmission. Results from in vivo microdialysis studies in freely moving animals have shown that DA receptor agonists or DA uptake inhibitors enhance 5‐HT release both within the DRN (Ferré et al ., 1994; Ferré & Artigas, 1993) and in its projection areas (Matsumoto et al ., 1996; Mendlin et al ., 1998). Moreover, lesions of midbrain DA neurons reduces 5‐HT outflow induced by behavioural and physiological stimuli (Mendlin et al ., 1999).…”

Section: Introductionmentioning

confidence: 99%

D₂‐like dopamine receptor activation excites rat dorsal raphe 5‐HT neurons in vitro

Haj‐Dahmane

2001

Eur J of Neuroscience

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The aim of the present study was to investigate the effect of dopamine (DA) on the excitability of dorsal raphe nucleus (DRN) 5-hydroxytryptamine (5-HT) neurons using the patch-clamp technique in brain slices. Bath application of DA (1-300 microM) produced a concentration-dependent membrane depolarization in all 5-HT neurons examined. This effect persisted in the presence of tetrodotoxin (TTX; 1 microM) and low extracellular calcium. Moreover, blockade of ionotropic glutamate receptors with 6,7-dinitroquinoxaline-2,3-dione (DNQX) and 2-amino-5-phosphonopentanoic acid (AP5) did not prevent DA-induced depolarization, indicating that it was mediated by a direct effect of DA on 5-HT neurons. The DA-induced depolarization was not antagonized by selective alpha1-adrenergic receptor antagonists, prazosin and WB 4101, but by a nonselective DA receptor antagonist, haloperidol. In addition, the selective D2-like receptor agonist quinpirole and antagonist sulpiride mimicked and blocked DA-induced depolarization, respectively. These results indicate that DA-induced membrane depolarization in DRN 5-HT neurons is mediated by the activation of D2-like DA receptors. The DA-induced membrane depolarization and inward current were associated with an increase in membrane conductance. Examination of the current-voltage (I-V) relationship for the DA-induced inward current revealed that the amplitude of the current increased with membrane hyperpolarization and reversed polarity at a potential near -15 mV. These data suggest that DA-induced depolarization in DRN 5-HT neurons is not mediated by a decrease in potassium conductance, but most likely by the activation of a nonselective cation current.

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“…DOI: 10.1002/hup on the serotonergic system have been shown by anatomical, retrograde labeling (Kalen et al, 1989;Peyron et al, 1996), and in vivo mycrodialysis studies (Guan and McBride, 1989;Ferre and Artigas, 1993;Ferre et al, 1994;Mendlin et al, 1998;Martin-Ruiz et al, 2001). Mendlin et al (1998) showed that the systemic administration of the non-selective dopamine receptor agonist apomorphine results in an increased efflux of serotonin in the striatum and hippocampus of freely moving rats (Mendlin et al, 1998). The serotonin output in dorsal raphe serotonergic neurons is also increased by administration of apomorphine (Martin-Ruiz et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Association of catechol‐O‐methyltransferase variants with loudness dependence of auditory evoked potentials

Juckel

Kawohl

Giegling

et al. 2007

Human Psychopharmacology

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Involvement of dopamine D2 receptors in apomorphine-induced facilitation of forebrain serotonin output

Cited by 26 publications

References 32 publications

The Effects of LPM570065, a Novel Triple Reuptake Inhibitor, on Extracellular Serotonin, Dopamine and Norepinephrine Levels in Rats

The Effects of LPM570065, a Novel Triple Reuptake Inhibitor, on Extracellular Serotonin, Dopamine and Norepinephrine Levels in Rats

D₂‐like dopamine receptor activation excites rat dorsal raphe 5‐HT neurons in vitro

Association of catechol‐O‐methyltransferase variants with loudness dependence of auditory evoked potentials

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Involvement of dopamine D2 receptors in apomorphine-induced facilitation of forebrain serotonin output

Cited by 26 publications

References 32 publications

The Effects of LPM570065, a Novel Triple Reuptake Inhibitor, on Extracellular Serotonin, Dopamine and Norepinephrine Levels in Rats

The Effects of LPM570065, a Novel Triple Reuptake Inhibitor, on Extracellular Serotonin, Dopamine and Norepinephrine Levels in Rats

D2‐like dopamine receptor activation excites rat dorsal raphe 5‐HT neurons in vitro

Association of catechol‐O‐methyltransferase variants with loudness dependence of auditory evoked potentials

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D₂‐like dopamine receptor activation excites rat dorsal raphe 5‐HT neurons in vitro