Modulation of GABA release from the thalamic reticular nucleus by cocaine and caffeine: Role of serotonin receptors
Serotonin receptors are targets of drug therapies for a variety of neuropsychiatric and neurodegenerative disorders. Cocaine inhibits the re-uptake of serotonin (5-HT), dopamine, and noradrenaline, whereas caffeine blocks adenosine receptors and opens ryanodine receptors in the endoplasmic reticulum...
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| Autores principales: | , |
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2016
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00223042_v136_n3_p526_Goitia http://hdl.handle.net/20.500.12110/paper_00223042_v136_n3_p526_Goitia |
| Aporte de: |
| Sumario: | Serotonin receptors are targets of drug therapies for a variety of neuropsychiatric and neurodegenerative disorders. Cocaine inhibits the re-uptake of serotonin (5-HT), dopamine, and noradrenaline, whereas caffeine blocks adenosine receptors and opens ryanodine receptors in the endoplasmic reticulum. We studied how 5-HT and adenosine affected spontaneous GABAergic transmission from thalamic reticular nucleus. We combined whole-cell patch clamp recordings of miniature inhibitory post-synaptic currents (mIPSCs) in ventrobasal thalamic neurons during local (puff) application of 5-HT in wild type (WT) or knockout mice lacking 5-HT 2A receptors (5-HT 2A -/-). Inhibition of mIPSCs frequency by low (10 μM) and high (100 μM) 5-HT concentrations was observed in ventrobasal neurons from 5-HT 2A -/- mice. In WT mice, only 100 μM 5-HT significantly reduced mIPSCs frequency. In 5-HT 2A -/- mice, NAN-190, a specific 5-HT 1A antagonist, prevented the 100 μM 5-HT inhibition while blocking H-currents that prolonged inhibition during post-puff periods. The inhibitory effects of 100 μM 5-HT were enhanced in cocaine binge-treated 5-HT 2A -/- mice. Caffeine binge treatment did not affect 5-HT-mediated inhibition. Our findings suggest that both 5-HT 1A and 5-HT 2A receptors are present in pre-synaptic thalamic reticular nucleus terminals. Serotonergic-mediated inhibition of GABA release could underlie aberrant thalamocortical physiology described after repetitive consumption of cocaine. Our findings suggest that both 5-HT 1A , 5-HT 2A and A1 receptors are present in pre-synaptic TRN terminals. 5-HT 1A and A1 receptors would down-regulate adenylate cyclase, whereas 5-HT 1A would also increase the probability of the opening of G-protein-activated inwardly rectifying K + channels (GIRK). Sustained opening of GIRK channels would hyperpolarize pre-synaptic terminals activating H-currents, resulting in less GABA release. 5-HT 2A -would activate PLC and IP 3 , increasing intracellular [Ca 2+ ] and thus facilitating GABA release. Our findings suggest that both 5-HT 1A , 5-HT 2A and A1 receptors are present in pre-synaptic TRN terminals. 5-HT 1A and A1 receptors would down-regulate adenylate cyclase, whereas 5-HT 1A would also increase the probability of the opening of G-protein-activated inwardly rectifying K + channels (GIRK). Sustained opening of GIRK channels would hyperpolarize pre-synaptic terminals activating H-currents, resulting in less GABA release. 5-HT 2A -would activate PLC and IP 3 , increasing intracellular [Ca 2+ ] and thus facilitating GABA release. © 2015 International Society for Neurochemistry. |
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