Caffeine Improves GABA Transport in the Striatum of Spontaneously Hypertensive Rats (SHR)
| Autor: | Danielle Dias Pinto Ferreira, Ricardo Augusto de Melo Reis, Mariana Nunes Marinho Ritter Ferreira, Pâmella de Moura, Maurício Dos Santos Pereira, Gustavo C. Ferreira, Thais da Rosa Valli, Regina Célia Cussa Kubrusly, Vladimir Pedro Borges-Martins, Robertta Silva Martins, Alex C. Manhães, Matheus F. Sathler |
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| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty Blotting Western Striatum Toxicology Adenosine A1 receptor chemistry.chemical_compound Spontaneously hypertensive rat Caffeine Rats Inbred SHR Internal medicine medicine Animals Rats Wistar gamma-Aminobutyric Acid Chemistry General Neuroscience Antagonist Adenosine Adenosine receptor Corpus Striatum Rats Endocrinology nervous system GABAergic Central Nervous System Stimulants Female medicine.drug |
| Zdroj: | Neurotoxicity Research. 39:1946-1958 |
| ISSN: | 1476-3524 1029-8428 |
| DOI: | 10.1007/s12640-021-00423-0 |
| Popis: | The spontaneously hypertensive rat (SHR) is an excellent animal model that mimics the behavioral and neurochemical phenotype of attention-deficit/hyperactivity disorder (ADHD). Here, we characterized the striatal GABA transport of SHR and investigated whether caffeine, a non-selective antagonist of adenosine receptors, could influence GABAergic circuitry. For this purpose, ex vivo striatal slices of SHR and Wistar (control strain) on the 35th postnatal day were dissected and incubated with [3H]-GABA to quantify the basal levels of uptake and release. SHR exhibited a reduced [3H]-GABA uptake and release, suggesting a defective striatal GABAergic transport system. GAT-1 appears to be the primary transporter for [3H]-GABA uptake in SHR striatum, as GAT-1 selective blocker, NO-711, completely abolished it. We also verified that acute exposure of striatal slices to caffeine improved [3H]-GABA uptake and release in SHR, whereas Wistar rats were not affected. GABA-uptake increase and cAMP accumulation promoted by caffeine was reverted by A1R activation with N6-cyclohexyl adenosine (CHA). As expected, the pharmacological blockade of cAMP-PKA signaling by H-89 also prevented caffeine-mediated [3H]-GABA uptake increment. Interestingly, a single caffeine exposure did not affect GAT-1 or A1R protein density in SHR, which was not different from Wistar protein levels, suggesting that the GAT-1-dependent transport in SHR has a defective functional activity rather than lower protein expression. The current data support that caffeine regulates GAT-1 function and improves striatal GABA transport via A1R-cAMP-PKA signaling, specifically in SHR. These results reinforce that caffeine may have therapeutic use in disorders where the GABA transport system is impaired. |
| Databáze: | OpenAIRE |
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