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Serotonin 5-HT 1A , 5-HT 2A and dopamine D 2 receptors strongly influence prefronto-hippocampal neural networks in alert mice: Contribution to the actions of risperidone.
- Source :
-
Neuropharmacology [Neuropharmacology] 2019 Nov 01; Vol. 158, pp. 107743. Date of Electronic Publication: 2019 Aug 17. - Publication Year :
- 2019
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Abstract
- Atypical antipsychotic drugs (APDs) used to treat positive and negative symptoms in schizophrenia block serotonin receptors 5-HT <subscript>2A</subscript> R and dopamine receptors D <subscript>2</subscript> R and stimulate 5-HT <subscript>1A</subscript> R directly or indirectly. However, the exact cellular mechanisms mediating their therapeutic actions remain unresolved. We recorded neural activity in the prefrontal cortex (PFC) and hippocampus (HPC) of freely-moving mice before and after acute administration of 5-HT <subscript>1A</subscript> R, 5-HT <subscript>2A</subscript> R and D <subscript>2</subscript> R selective agonists and antagonists and atypical APD risperidone. We then investigated the contribution of the three receptors to the actions of risperidone on brain activity via statistical modeling and pharmacological reversal (risperidone + 5-HT <subscript>1A</subscript> R antagonist WAY-100635, risperidone + 5-HT <subscript>2A/2C</subscript> R agonist DOI, risperidone + D <subscript>2</subscript> R agonist quinpirole). Risperidone, 5-HT <subscript>1A</subscript> R agonism with 8-OH-DPAT, 5-HT <subscript>2A</subscript> R antagonism with M100907, and D <subscript>2</subscript> R antagonism with haloperidol reduced locomotor activity of mice that correlated with a suppression of neural spiking, power of theta and gamma oscillations in PFC and HPC, and reduction of PFC-HPC theta phase synchronization. By contrast, activation of 5-HT <subscript>2A</subscript> R with DOI enhanced high-gamma oscillations in PFC and PFC-HPC high gamma functional connectivity, likely related to its hallucinogenic effects. Together, power changes, regression modeling and pharmacological reversals suggest an important role of 5-HT <subscript>1A</subscript> R agonism and 5-HT <subscript>2A</subscript> R antagonism in risperidone-induced alterations of delta, beta and gamma oscillations, while D <subscript>2</subscript> R antagonism may contribute to risperidone-mediated changes in delta oscillations. This study provides novel insight into the neural mechanisms for widely prescribed psychiatric medication targeting the serotonin and dopamine systems in two regions involved in the pathophysiology of schizophrenia.<br /> (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Subjects :
- 8-Hydroxy-2-(di-n-propylamino)tetralin pharmacology
Amphetamines pharmacology
Animals
Brain Waves drug effects
Cortical Synchronization drug effects
Dopamine Agonists pharmacology
Dopamine Antagonists pharmacology
Electroencephalography
Fluorobenzenes pharmacology
Gamma Rhythm drug effects
Haloperidol pharmacology
Hippocampus metabolism
Mice
Neural Pathways drug effects
Piperazines pharmacology
Piperidines pharmacology
Prefrontal Cortex metabolism
Pyridines pharmacology
Quinpirole pharmacology
Receptor, Serotonin, 5-HT1A metabolism
Receptor, Serotonin, 5-HT2A metabolism
Receptors, Dopamine D2 metabolism
Serotonin Antagonists pharmacology
Serotonin Receptor Agonists pharmacology
Antipsychotic Agents pharmacology
Hippocampus drug effects
Locomotion drug effects
Prefrontal Cortex drug effects
Receptor, Serotonin, 5-HT1A drug effects
Receptor, Serotonin, 5-HT2A drug effects
Receptors, Dopamine D2 drug effects
Risperidone pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-7064
- Volume :
- 158
- Database :
- MEDLINE
- Journal :
- Neuropharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 31430459
- Full Text :
- https://doi.org/10.1016/j.neuropharm.2019.107743