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Modulation of GABA release from the thalamic reticular nucleus by cocaine and caffeine: role of serotonin receptors.
Goitia, Belén; Rivero-Echeto, María Celeste; Weisstaub, Noelia V; Gingrich, Jay A; Garcia-Rill, Edgar; Bisagno, Verónica; Urbano, Francisco J.
Afiliação
  • Goitia B; Departamento de Fisiología, Biología Molecular y Celular "Dr. Héctor Maldonado" (DFBMC) Facultad de Ciencias Exactas y Naturales, Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE-CONICET-UBA), Universidad de Buenos Aires, Ciudad Universitaria, Ciudad de Buenos Aires, Argentina.
  • Rivero-Echeto MC; Facultad de Farmacia y Bioquímica, Instituto de Investigaciones Farmacológicas (ININFA-UBA-CONICET), Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina.
  • Weisstaub NV; Departamento de Fisiología, Biología Molecular y Celular "Dr. Héctor Maldonado" (DFBMC) Facultad de Ciencias Exactas y Naturales, Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE-CONICET-UBA), Universidad de Buenos Aires, Ciudad Universitaria, Ciudad de Buenos Aires, Argentina.
  • Gingrich JA; Facultad de Farmacia y Bioquímica, Instituto de Investigaciones Farmacológicas (ININFA-UBA-CONICET), Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina.
  • Garcia-Rill E; Grupo de Neurociencia de Sistemas, Departamento de Fisiología, Facultad de Medicina, Instituto de Fisiología y Biofísica (IFIBIO), UBA, Ciudad de Buenos Aires, Argentina.
  • Bisagno V; Division of Developmental Neuroscience, Columbia University and the NYSPI, Sackler Institute for Developmental Psychobiology, New York City, New York, USA.
  • Urbano FJ; Department of Neurobiology and Developmental Sciences, Center for Translational Neuroscience, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
J Neurochem ; 136(3): 526-35, 2016 Feb.
Article em En | MEDLINE | ID: mdl-26484945
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-HT2A receptors (5-HT2A -/-). Inhibition of mIPSCs frequency by low (10 µM) and high (100 µM) 5-HT concentrations was observed in ventrobasal neurons from 5-HT2A -/- mice. In WT mice, only 100 µM 5-HT significantly reduced mIPSCs frequency. In 5-HT2A -/- mice, NAN-190, a specific 5-HT1A 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-HT2A -/- mice. Caffeine binge treatment did not affect 5-HT-mediated inhibition. Our findings suggest that both 5-HT1A and 5-HT2A 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-HT1A , 5-HT2A and A1 receptors are present in pre-synaptic TRN terminals. 5-HT1A and A1 receptors would down-regulate adenylate cyclase, whereas 5-HT1A 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-HT2A -would activate PLC and IP3 , increasing intracellular [Ca(2+) ] and thus facilitating GABA release.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Inibidores de Fosfodiesterase / Núcleos Talâmicos / Cafeína / Cocaína / Inibidores da Captação de Dopamina / Receptor 5-HT2A de Serotonina / Ácido gama-Aminobutírico Limite: Animals Idioma: En Revista: J Neurochem Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Argentina País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Inibidores de Fosfodiesterase / Núcleos Talâmicos / Cafeína / Cocaína / Inibidores da Captação de Dopamina / Receptor 5-HT2A de Serotonina / Ácido gama-Aminobutírico Limite: Animals Idioma: En Revista: J Neurochem Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Argentina País de publicação: Reino Unido