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- Title
Preferential Modulatory Action of 5-HT<sub>2A</sub> Receptors on the Dynamic Regulation of Basal Ganglia Circuits.
- Authors
Guilhemsang, Lise; Gutierrez-Ceballos, Amaia; Antonazzo, Mario; Mallet, Nicolas P.; Ugedo, Luisa; Morera-Herreras, Teresa
- Abstract
In rodents, cortical information is transferred to the substantia 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-HT2A receptors 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-HT2A receptors could have a specific signature on the dynamic regulation of BG circuits, preferentially modulating the mPF information processing through trans-striatal pathways. We performed in vivo single-unit extracellular recordings to assess the effect of the 5-HT2A agonist 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 mg/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-HT2A receptor antagonist MDL11939 (200 mg/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-HT2A receptors have a preferential modulatory action on the dynamic regulation of BG circuitry.
- Subjects
BASAL ganglia; NEURAL circuitry; SUBTHALAMIC nucleus; SUBSTANTIA nigra; METHYL formate; RAPHE nuclei
- Publication
Journal of Neuroscience, 2023, Vol 43, Issue 1, p56
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.1181-22.2022