Single Cocaine Exposure Inhibits GABA Uptake via Dopamine D1-Like Receptors in Adolescent Mice Frontal Cortex
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ORIGINAL ARTICLE
Single Cocaine Exposure Inhibits GABA Uptake via Dopamine D1-Like Receptors in Adolescent Mice Frontal Cortex Regina Célia Cussa Kubrusly 1 & Robertta Silva Martins 1 & Lisiane de Santana Souza 2 & Mariana Pinheiro de Carvalho 1 & Vladimir Pedro Peralva Borges-Martins 1 & Matheus Figueiredo Sathler 3 & Danielle Dias Pinto Ferreira 4 & Maurício dos Santos Pereira 5 & Ney Ronner Peccinalli 1 & Pablo Pandolfo 2 & Ricardo Augusto de Melo Reis 6 & Gustavo Costa Ferreira 7 & Alex Christian Manhães 8 Received: 9 April 2020 / Revised: 29 June 2020 / Accepted: 13 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Cocaine (COC) is a psychostimulant that acts by increasing catecholaminergic neurotransmission mainly due to its effects on the dopamine transporter (DAT). However, other neurotransmitter systems may also be regulated by COC, including the GABAergic system. Since the effect of COC in modulating gamma-aminobutyric acid (GABA) reuptake is not defined, we investigated the molecular mechanisms related to the increase in GABA uptake induced by acute COC exposure and its effects on locomotor activity in adolescent mice. Behavioral experiments showed that COC increased locomotor activity and decreased immobilization time in mice. A single COC exposure reduced both GABA uptake and GAT-1 protein levels. On the other hand, cyclic adenosine monophosphate (cAMP) levels increased after a COC challenge. The major changes induced by acute COC on behavioral and neurochemical assays were avoided by previous treatment with the selective D1 receptor antagonist SCH-23390 (0.5 mg/kg). Our findings suggest that GABA uptake naturally decreases during mice development from preadolescence until adulthood and that dopamine (DA) D1-like receptors are key players in the regulation of GABA uptake levels following a single COC exposure in adolescent mice. Keywords Cocaine . GABA . Mice . GAT-1 . D1-like receptors
Abbreviations 5-HT Serotonin AMPA α-Amino-3-hydroxy-5-methyl-4isoxazolepropionic acid BAC Bacterial artificial chromosome. cAMP Cyclic adenosine monophosphate
CNS COC D1R DA FC GABA
* Regina Célia Cussa Kubrusly [email protected]; [email protected]
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Laboratório de Neurofisiologia Molecular, Departamento de Morfologia, Fisiologia e Patologia Básica, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil
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Laboratório de Neuroquímica, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
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Laboratório de Neuroenergética e Erros Inatos do Metabolismo, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
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Laboratório de Neurofisiologia, Instituto de Biologia, Universidade Estadual do Rio de Janeiro, Rio de Janeiro, Brazil
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Laboratório de Neurofarmacologia, Instituto Biomédico - Bloco E, Rua São João Batista 187, sala 428, Centro, Niteroi, RJ CEP 24020-005, Brazil Laboratório de Neurobiologia do Comporta
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