The somatodendritic release of dopamine in the ventral tegmental area and its regulation by afferent transmitter systems

Adell, Albert; Artigas, Francesc

doi:10.1016/j.neubiorev.2004.05.001

Cited by 156 publications

(117 citation statements)

References 271 publications

(252 reference statements)

Supporting

Mentioning

112

Contrasting

Unclassified

Order By: Relevance

“…Although these receptors bear little sequence homology and their expression patterns are quite different, both are regulated by the same transcription factor, Freud-1. Interestingly, both receptors function as pre-synaptic autoreceptors to regulate serotonin and dopamine neurotransmission, respectively (11,42). Thus, Freud-1 may coordinately regulate the activity of these two systems implicated in behavioral control.…”

Section: Freud-1 Mediated Repression Of the Dopamine-d2mentioning

confidence: 99%

Differential Repression by Freud-1/CC2D1A at a Polymorphic Site in the Dopamine-D2 Receptor Gene

Rogaeva

Jafar‐Nejad

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

Freud-1/CC2D1A is a transcriptional repressor of the serotonin-1A receptor gene and was recently genetically linked to non-syndromic mental retardation. To identify new Freud-1 gene targets, data base mining for Freud-1 recognition sequences was done. A highly homologous intronic element (D2-DRE) was identified in the human dopamine-D2 receptor (DRD2) gene, and the role of Freud-1 in regulating the gene at this site was assessed. Recombinant Freud-1 bound specifically to the D2-DRE, and a major protein-D2-DRE complex was identified in nuclear extracts that was supershifted using Freud-1-specific antibodies. Endogenous Freud-1 binding to the D2-DRE in cells was detected using chromatin immunoprecipitation. The D2-DRE conferred strong repressor activity in transcriptional reporter assays that was dependent on the Freud-1 recognition sequence. In three different human cell lines, the level of Freud-1 protein was inversely related to DRD2 expression. Knockdown of endogenous Freud-1 using small interfering RNA resulted in an up-regulation of DRD2 RNA and binding sites, demonstrating a crucial role for Freud-1 in DRD2 regulation. A previously uncharacterized single nucleotide A/G polymorphism (rs2734836) was located adjacent to the D2-DRE and conferred allele-specific Freud-1 binding and repression, with the major G-allele having reduced activity. These studies demonstrate a key role for Freud-1 to regulate DRD2 expression and provide the first mechanistic insights into its transcriptional regulation. Allele-specific regulation of DRD2 expression by Freud-1 may possibly associate with psychiatric disorders or mental retardation.Dopamine-D2 receptors function as both pre-synaptic autoreceptors and post-synaptic receptors, and play key roles in regulating dopaminergic neurotransmission. Increased levels of dopamine-D2 receptors or dopaminergic hyperactivity have been implicated in schizophrenia (1-3), and most antipsychotic drugs inhibit dopamine-D2 receptors (4 -6). Although transcriptional regulation of the rat dopamine D2 receptor (DRD2) 5 gene has been examined, very little is known regarding the regulation of the human DRD2 gene. A polymorphism in the putative DRD2 promoter confers decreased transcriptional activity and has been negatively associated with schizophrenia (7). However, the transcriptional mechanisms for regulation of the human DRD2 gene have yet to be elucidated.To identify new transcriptional regulators in the nervous system, we previously characterized the serotonin-1A (5-HT1A) receptor promoter region and identified a novel dual repressor element (DRE) that negatively regulates its expression (8, 9). The DRE consists of adjacent and partially overlapping repressor elements: 5Ј-repressor element (FRE; major regulator in neuronal cells) and 3Ј-repressor element (9). Analysis of DREbinding proteins revealed that a novel protein, Freud-1 (Five prime repressor under dual repression-binding protein-1)/ CC2D1A (Coiled-coil and C2 Domain containing 1A) binds to and represses the 5-HT1A receptor gene throug...

show abstract

Section: Freud-1 Mediated Repression Of the Dopamine-d2mentioning

confidence: 99%

Differential Repression by Freud-1/CC2D1A at a Polymorphic Site in the Dopamine-D2 Receptor Gene

Rogaeva

Jafar‐Nejad

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Interestingly, neither agent affected DA levels in striatum or nucleus accumbens which are innervated by different subpopulations of dopaminergic cell bodies: that is, substantia nigra pars compacta (nigrostriatal) and paranigral-VTA (mesolimbic) vs parabrachial-VTA (mesocortical), respectively (Lejeune et al, 1997; Lejeune and Millan, 2000). These observations accord with the differential control of these clusters of dopaminergic neurons Adell and Artigas, 2004;Alex and Pehek, 2007), including 5-HT 1A receptor agonism which disinhibits VTA-derived mesocortical dopaminergic and LC-derived adrenergic pathways via GABAergic interneurones Invernizzi et al, 2007). Interestingly, 8-OH-DPAT and S15535-induced elevations in FCX levels of DA and NA (Millan et al, 1997b;Gobert et al, 1995Gobert et al, , 1999, were additive to those of GR205171.…”

Section: Discussion Potentiation By Gr205171 Of the Influence Of Citamentioning

confidence: 92%

Neurokinin1 Antagonists Potentiate Antidepressant Properties of Serotonin Reuptake Inhibitors, Yet Blunt Their Anxiogenic Actions: A Neurochemical, Electrophysiological, and Behavioral Characterization

Gobert

Brocco

Dekeyne

et al. 2008

Neuropsychopharmacol

View full text Add to dashboard Cite

Though neurokinin 1 (NK 1 ) receptor antagonists are active in experimental models of depression, clinical efficacy has proven disappointing. This encourages interest in association of NK 1 receptor blockade with inhibition of serotonin (5-HT) reuptake. The selective NK 1 antagonist, GR205171, dose-dependently enhanced citalopram-induced elevations of extracellular levels of 5-HT in frontal cortex, an action expressed stereospecifically vs its less active distomer, GR226206. Further, increases in 5-HT levels in dorsal hippocampus, basolateral amygdala, nucleus accumbens, and striatum were likewise potentiated, and GR205171 similarly facilitated the influence of fluoxetine upon levels of 5-HT, as well as dopamine and noradrenaline. In parallel electrophysiological studies, the inhibitory influence of citalopram and fluoxetine upon raphe-localized serotonergic neurones was stereospecifically blunted by GR205171. Antidepressant actions of citalopram in a forced-swim test in mice were stereospecifically potentiated by GR205171, and it also enhanced attenuation by citalopram of stress-related ultrasonic vocalizations in rats. Further, GR205171 and citalopram additively abrogated the advance in circadian rhythms provoked by exposure to light in hamsters. By contrast, GR205171 stereospecifically blocked anxiogenic actions of citalopram in social interaction procedures in rats and gerbils, and stereospecifically abolished facilitation of fearinduced foot tapping by fluoxetine in gerbils. By analogy to GR205171, a further NK 1 antagonist, RP67580, enhanced the influence of citalopram upon frontocortical levels of 5-HT and potentiated its actions in the forced swim test. In conclusion, NK 1 receptor blockade differentially modulates functional actions of SSRIs: antidepressant properties are reinforced, whereas anxiogenic effects are attenuated. Combined NK 1 receptor antagonism/5-HT reuptake inhibition may offer advantages in the management of depressed and anxious states.

show abstract

“…D 2 receptor desensitisation is not normally apparent when agonists are used to inhibit dopamine neuron firing in vitro (Fig. 1) (Bowery et al, 1994;Mercuri et al, 1997;Centonze et al, 2002) or in vivo (Bunney et al, 1973;White & Wang, 1984;Kalivas et al, 1993;Sibley et al, 1993;Adell & Artigas, 2004), in agreement with their role of providing essential feedback autoinhibition on dopamine neurons. However, desensitisation can be induced with high concentrations of agonists (Beckstead & Williams, 2007), in particular with accumulative dosing (Fig.…”

Section: Potency Of Quinpirole On Dopamine Neuron Firing Is Similar Bmentioning

confidence: 83%

“…Synchronized high-frequency stimulation of dopamine neurons can activate D 2 receptors by increasing somatodendritic release of dopamine (Bunney et al, 1973;White & Wang, 1984;Sibley et al, 1993;Mercuri et al, 1997;Adell & Artigas, 2004), with the resultant inhibitory current inhibits the firing of dopamine neurons generating a "pause" of firing (Beckstead et al, 2004). The presence of D 2 receptor antagonist haloperidol, therefore, impaired burst by inducing depolarization block of firing (Grace & Bunney, 1986).…”

Section: Potency Of Quinpirole On Dopamine Neuron Firing Is Similar Bmentioning

confidence: 99%

“…In addition, the VTA is suggested to be the site important for the development of sensitization to repeated exposures to drugs of abuse, via effects of dopamine on dopamine receptors (Wise, 1996) and neuroplastic changes at glutamatergic synapses (Bonci & Malenka, 1999 (Bouthenet et al, 1987;Wamsley et al, 1989;Chen et al, 1991;Adell & Artigas, 2004), where activation of D 2 receptors inhibits the firing activity of dopamine neurons, carrying out an important autoinhibitory function (Bunney et al, 1973;White & Wang, 1984;Sibley et al, 1993;Mercuri et al, 1997;Adell & Artigas, 2004). …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Increased desensitization of dopamine D2 receptor-mediated response in the ventral tegmental area in the absence of adenosine A2A receptors

Al‐Hasani

Metaxas

et al. 2011

Neuroscience

View full text Add to dashboard Cite

The somatodendritic release of dopamine in the ventral tegmental area and its regulation by afferent transmitter systems

Cited by 156 publications

References 271 publications

Differential Repression by Freud-1/CC2D1A at a Polymorphic Site in the Dopamine-D2 Receptor Gene

Differential Repression by Freud-1/CC2D1A at a Polymorphic Site in the Dopamine-D2 Receptor Gene

Neurokinin1 Antagonists Potentiate Antidepressant Properties of Serotonin Reuptake Inhibitors, Yet Blunt Their Anxiogenic Actions: A Neurochemical, Electrophysiological, and Behavioral Characterization

Increased desensitization of dopamine D2 receptor-mediated response in the ventral tegmental area in the absence of adenosine A2A receptors

Contact Info

Product

Resources

About