5-HT2A Receptors in the Basal Ganglia

Miguélez, Cristina; Morera-Herreras, Teresa; Deurwaerdère, Philippe De

doi:10.1007/978-3-319-70474-6_12

Cited by 3 publications

(1 citation statement)

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“…Moreover, the authors did not protect the possible binding of ketanserin on the "tetrabenazine" site (monoamine vesicular transporter), which could contribute to the effects, particularly in brain regions densely innervated with monoaminergic neurons [45,46]. On the other hand, IHC is more of a qualitative approach at variance with quantitative autoradiographic studies.…”

Section: Discussionmentioning

confidence: 99%

Acute and Chronic Nicotine Exposures Differentially Affect Central Serotonin 2A Receptor Function: Focus on the Lateral Habenula

Bombardi

Delicata

Tagliavia

et al. 2020

IJMS

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Nicotine addiction is a serious public health problem causing millions of deaths worldwide. Serotonin (5-hydroxytryptamine; 5-HT) is involved in central nervous system (CNS) nicotine effects, and it has been suggested as a promising pharmacological target for smoking cessation. In this regard, what is particularly interesting are the 5-HT2A receptors (5-HT2ARs) and the lateral habenula (LHb), a central area in nicotine addiction that we showed to be under a strong 5-HT2AR-modulation. Single-cell extracellular recording of LHb neurons was used to study the 5-HT2AR function by intravenously administrating the potent agonist TCB-2. Acute nicotine (2 mg/kg, intraperitoneal, i.p.) and chronic nicotine (6 mg/kg/day for 14 days) differently affected both the 5-HT2AR-immuno reactive (IR) neuron number and the 5-HT2AR immunostaining area in the different brain areas studied. After acute nicotine, TCB-2 cumulative doses (5–640 µg/kg, intravenous, i.v.) bidirectionally affected the activity of 74% of LHb recorded neurons. After chronic nicotine treatment, TCB-2 was only capable of decreasing the LHb firing rate. The expression of 5-HT2AR under acute and chronic nicotine exposure was studied in the LHb and in other brain areas involved in nicotine effects in rats by using immunohistochemistry. These data reveal that acute and chronic nicotine differentially affect the 5-HT2AR function in different brain areas and this might be relevant in nicotine addiction and its treatment.

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Section: Discussionmentioning

confidence: 99%

Acute and Chronic Nicotine Exposures Differentially Affect Central Serotonin 2A Receptor Function: Focus on the Lateral Habenula

Bombardi

Delicata

Tagliavia

et al. 2020

IJMS

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Contributions of Basal Ganglia Circuits to Perception, Attention, and Consciousness

Redinbaugh,

Saalmann

2024

Journal of Cognitive Neuroscience

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Research into ascending sensory pathways and cortical networks has generated detailed models of perception. These same cortical regions are strongly connected to subcortical structures, such as the basal ganglia (BG), which have been conceptualized as playing key roles in reinforcement learning and action selection. However, because the BG amasses experiential evidence from higher and lower levels of cortical hierarchies, as well as higher-order thalamus, it is well positioned to dynamically influence perception. Here, we review anatomical, functional, and clinical evidence to demonstrate how the BG can influence perceptual processing and conscious states. This depends on the integrative relationship between cortex, BG, and thalamus, which allows contributions to sensory gating, predictive processing, selective attention, and representation of the temporal structure of events.

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Preferential Modulatory Action of 5-HT_2AReceptors on the Dynamic Regulation of Basal Ganglia Circuits

et al. 2022

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In rodents, cortical information is transferred to thesubstantia nigra pars reticulata(SNr) through motor and medial prefrontal (mPF) basal ganglia (BG) circuits implicated in motor and cognitive/motivational behaviors, respectively. The serotonergic 5-HT2Areceptors are located in both of these neuronal networks, displaying topographical differences with a high expression in the associative/limbic territories, and a very low expression in the subthalamic nucleus. This study investigated whether the stimulation of 5-HT2Areceptors could have a specific signature on the dynamic regulation of BG circuits, preferentially modulating the mPF information processing through trans-striatal pathways. We performedin vivosingle-unit extracellular recordings to assess the effect of the 5-HT2Aagonist TCB-2 on the spontaneous and cortically evoked activity of lateral and medial SNr neurons in male rats (involved in motor and mPF circuits, respectively). TCB-2 (50–200 µg/kg, i.v.) increased the basal firing rate and enhanced the cortically evoked inhibitory response of medial SNr neurons (transmission through the direct striato-nigral pathway). A prior administration of the preferential 5-HT2Areceptor antagonist MDL11939 (200 µg/kg, i.v.) did not modify any electrophysiological parameter, but occluded TCB-2-induced effects. In animals treated with the 5-HT synthesis inhibitor pCPA (4-chloro-dl-phenylalanine methyl ester hydrochloride), TCB-2 failed to induce the above-mentioned effects, thus suggesting the contribution of endogenous 5-HT. However, the mobilization of 5-HT induced by the acute administration of fluoxetine (10 mg/kg, i.p.) did not mimic the effects triggered by TCB-2. Overall, these data suggest that 5-HT2Areceptors have a preferential modulatory action on the dynamic regulation of BG circuitry.SIGNIFICANCE STATEMENTMotor and medial prefrontal (mPF) basal ganglia (BG) circuits play an important role in integrative brain functions like movement control or cognitive/motivational behavior, respectively. Although these neuronal networks express 5-HT2Areceptors, the expression is higher in associative/limbic structures than in the motor ones. We show a topographical-dependent dissociation in the effects triggered by the 5HT2Aagonist TCB-2, which specifically increases the medialsubstantia nigra pars reticulataneuron activity and has a preferential action on mPF information processing through the striato-nigral direct pathway. These are very likely to be 5-HT2Areceptor-mediated effects that require mobilization of the endogenous 5-HT system. These findings provide evidence about the specific signature of 5-HT2Areceptors on the dynamic regulation of BG circuits.

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5-HT2A Receptors in the Basal Ganglia

Cited by 3 publications

References 272 publications

Acute and Chronic Nicotine Exposures Differentially Affect Central Serotonin 2A Receptor Function: Focus on the Lateral Habenula

Acute and Chronic Nicotine Exposures Differentially Affect Central Serotonin 2A Receptor Function: Focus on the Lateral Habenula

Contributions of Basal Ganglia Circuits to Perception, Attention, and Consciousness

Preferential Modulatory Action of 5-HT_2AReceptors on the Dynamic Regulation of Basal Ganglia Circuits

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5-HT2A Receptors in the Basal Ganglia

Cited by 3 publications

References 272 publications

Acute and Chronic Nicotine Exposures Differentially Affect Central Serotonin 2A Receptor Function: Focus on the Lateral Habenula

Acute and Chronic Nicotine Exposures Differentially Affect Central Serotonin 2A Receptor Function: Focus on the Lateral Habenula

Contributions of Basal Ganglia Circuits to Perception, Attention, and Consciousness

Preferential Modulatory Action of 5-HT2AReceptors on the Dynamic Regulation of Basal Ganglia Circuits

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Preferential Modulatory Action of 5-HT_2AReceptors on the Dynamic Regulation of Basal Ganglia Circuits