Pattern of expression of the serotonin2C receptor messenger RNA in the basal ganglia of adult rats

Eberle-Wang, K.; Mikeladze, Z. A.; Uryu, Kunihiro; Chesselet, Marie‐Françoise

doi:10.1002/(sici)1096-9861(19970728)384:2<233::aid-cne5>3.0.co;2-2

Cited by 224 publications

(129 citation statements)

References 54 publications

Supporting

Mentioning

120

Contrasting

Unclassified

Order By: Relevance

“…As for the cellular localization of 5-HT2C receptors in other regions, little is known. In the NA and striatum, the morphology of 5-HT2C mRNA containing cells indicates that they may be efferents, suggesting localization to GABAergic projection neurons (Eberle-Wang et al, 1997). This study also showed that 5-HT2C mRNA present in the SN and VTA did not colocalize with TH mRNA, a marker for DA neurons.…”

Section: -Ht2c Localizationmentioning

confidence: 55%

“…In-situ hybridization studies have demonstrated that 5-HT2C receptor mRNA is expressed in the VTA (Hoffman and Mezey, 1989;Molineaux et al, 1989;Pompeiano et al, 1994;Wright et al, 1995;Eberle-Wang et al, 1997), both the pars compacta and pars reticulata subdivisions of the SN (Molineaux et al, 1989;Pompeiano et al, 1994;Wright et al, 1995;Eberle-Wang et al, 1997), and in the terminal regions of the nigrostriatal and mesolimbic dopaminergic pathways: the striatum and the NA (Hoffman and Mezey, 1989;Pompeiano et al, 1994;Wright et al, 1995;Eberle-Wang et al, 1997). There is comparatively less evidence for 5-HT2C receptor mRNA in the PFC, however, several studies have shown the presence of 5-HT2C receptor mRNA in the cingulate or anterior cingulate cortex (Hoffman and Mezey, 1989;Pompeiano et al, 1994;Wright et al, 1995).…”

Section: -Ht2c Localizationmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Alex

Pehek

2007

Pharmacology & Therapeutics

536

311

View full text Add to dashboard Cite

The neurotransmitter dopamine (DA) has a long association with normal functions such as motor control, cognition, and reward, as well as a number of syndromes including drug abuse, schizophrenia, and Parkinson's disease. Studies show that serotonin (5-HT) acts through several 5-HT receptors in the brain to modulate DA neurons in all three major dopaminergic pathways. There are at least 14 5-HT receptor subtypes, many of which have been shown to play some role in mediating 5-HT/DA interactions. Several subtypes, including the 5-HT1A, 5-HT1B, 5-HT2A, 5-HT3 and 5-HT4 receptors, act to facilitate DA release, while the 5-HT2C receptor mediates an inhibitory effect of 5-HT on DA release. Most 5-HT receptor subtypes only modulate DA release when 5-HT and/or DA neurons are stimulated, but the 5-HT2C receptor, characterized by high levels of constitutive activity, inhibits tonic as well as evoked DA release. This review summarizes the anatomical evidence for the presence of each 5-HT receptor subtype in dopaminergic regions of the brain and the neuropharmacological evidence demonstrating regulation of each DA pathway. The relevance of 5-HT receptor modulation of DA systems to the development of therapeutics used to treat schizophrenia, depression, and drug abuse is discussed. Lastly, areas are highlighted in which future research would be maximally beneficial to the treatment of these disorders.

show abstract

Section: -Ht2c Localizationmentioning

confidence: 55%

Section: -Ht2c Localizationmentioning

confidence: 99%

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Alex

Pehek

2007

Pharmacology & Therapeutics

536

311

View full text Add to dashboard Cite

show abstract

“…Specifically, the pattern of 5-HT 2C R edited isoforms may determine the response to endogenous 5-HT (Herrick-Davis et al, 1999) and control the signal-tonoise ratio at central 5-HT synapses (Gurevich et al, 2002;Niswender et al, 1999). In the NAc, 5-HT 2C R, transcripts are densely expressed in the anterior compartment and appear to localize to medium-sized neurons that express the distribution, localization, and morphology typical of striatal GABA efferent neurons (Eberle-Wang et al, 1997;Morilak et al, 1993). Thus, the stimulation or blockade of 5-HT 2C Rs within the NAc might disrupt local GABA circuits and also negative feedback loops to the VTA.…”

Section: Discussionmentioning

confidence: 99%

Differential Regulation of the Mesoaccumbens Dopamine Circuit by Serotonin2C Receptors in the Ventral Tegmental Area and the Nucleus Accumbens: An In Vivo Microdialysis Study with Cocaine

Navailles

Moison

Cunningham

et al. 2007

Neuropsychopharmacol

100

102

View full text Add to dashboard Cite

Stimulation of central serotonin2C receptor (5-HT 2C R) inhibits dopamine (DA)-dependent neurochemical and behavioral effects of cocaine, while 5-HT 2C Rs locally expressed into the ventral tegmental area (VTA) and the nucleus accumbens (NAc) exert opposite functional control over cocaine-induced behavioral effects. Using in vivo microdialysis in halothane-anesthetized rats, we tested the hypothesis that this functionally opposite regulation of the mesoaccumbens DA pathway relies on the ability of 5-HT 2C Rs in the VTA and the NAc to inhibit and enhance respectively cocaine-induced accumbal DA outflow. Intra-VTA injection of the 5-HT 2C R agonist Ro 60-0175 at 5 mg/0.2 ml, but not 1 mg/0.2 ml, attenuated the increase in accumbal DA outflow induced by the systemic administration of 10 mg/ kg of cocaine. Intra-VTA injection of the 5-HT 2C R antagonist SB 242084 at either dose (0.1 or 0.5 mg/0.2 ml) did not modify the effects of cocaine. Intra-NAc application of Ro 60-0175 dose-dependently excited (0.1 mM) and inhibited (1 mM) cocaine-induced DA outflow. In contrast, intra-NAc application of SB 242084 resulted in diametrically opposite effects when applied at these concentrations. These results further support the idea that the overall action of central 5-HT 2C Rs on accumbal DA output is dependent, at least in part, on the functional balance between different 5-HT 2C R populations within the NAc and within the mesoaccumbens DA pathway (VTA vs NAc).

show abstract

“…48 It is also expressed in the major monoamine synthesizing areas including the locus coeruleus, raphe nuclei, substantia nigra and ventral tegmental area where it is known to regulate dopamine release. [48][49][50][51] Given the importance of these structures in modulating the emotional state, further investigation of the 5-HT 2C R mRNAediting status in these brain areas of suicide victims should be undertaken.…”

Section: Discussionmentioning

confidence: 99%

Increased serotonin 2C receptor mRNA editing: a possible risk factor for suicide

et al. 2007

View full text Add to dashboard Cite

Suicide is a major public health problem with B1 million victims each year worldwide. Up to 90% of adults who commit suicide have at least one psychiatric diagnosis such as major depression, bipolar disorder (BPD), schizophrenia (SZ), substance abuse or dependence. A question that has remained unanswered is whether the biological substrates of suicide are distinct from those of the psychiatric disorders in which it occurs. The serotonin 2C receptor (5-HT 2C R) has been implicated in depression and suicide. We, therefore, compared the frequencies of its mRNA editing variants in postmortem prefrontal cortical specimens from subjects who committed suicide or who died from other causes. All suicides occurred in the context of either SZ or BPD. The non-suicide cases included subjects with either SZ or BPD as well as subjects with no psychiatric diagnosis. We identified 5-HT 2C R mRNA editing variations that were associated with suicide but not with the comorbid psychiatric diagnoses, and were not influenced by demographic characteristics (age and sex) and alcohol or drug use. These variations consisted of a significant increase in the pool of mRNA variants (ACD and ABCD) that encode one of the most prevalent and highly edited isoforms of 5-HT 2C R, that is, VSV (Val156-Ser158-Val160). Because the VSV isoform of 5-HT 2C R exhibits low functional activity, an increase in its expression frequency may significantly influence the serotonergic regulation of the brain. Thus, at least in patients with SZ or BPD, overexpression of the VSV isoform in the prefrontal cortex may represent an additional risk factor for suicidal behavior.

show abstract

Pattern of expression of the serotonin2C receptor messenger RNA in the basal ganglia of adult rats

Cited by 224 publications

References 54 publications

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Differential Regulation of the Mesoaccumbens Dopamine Circuit by Serotonin2C Receptors in the Ventral Tegmental Area and the Nucleus Accumbens: An In Vivo Microdialysis Study with Cocaine

Increased serotonin 2C receptor mRNA editing: a possible risk factor for suicide

Contact Info

Product

Resources

About