title: Caffeine Reverts Memory But Not Mood Impairment in a Depression-Prone Mouse Strain with Up-Regulated Adenosine A2AReceptor in Hippocampal Glutamate Synapses.
abstract: Caffeine prophylactically prevents mood and memory impairments through adenosine A2Areceptor (A2AR) antagonism. A2AR antagonists also therapeutically revert mood and memory impairments, but it is not known if caffeine is also therapeutically or only prophylactically effective. Since depression is accompanied by mood and memory alterations, we now explored if chronic (4 weeks) caffeine consumption (0.3 g/L) reverts mood and memory impairment in helpless mice (HM, 12 weeks old), a bred-based model of depression. HM displayed higher immobility in the tail suspension and forced swimming tests, greater anxiety in the elevated plus maze, and poorer memory performance (modified Y-maze and object recognition). HM also had reduced density of synaptic (synaptophysin, SNAP-25), namely, glutamatergic (vGluT1; -22 ± 7 %) and GABAergic (vGAT; -23 ± 8 %) markers in the hippocampus. HM displayed higher A2AR density (72 ± 6 %) in hippocampal synapses, an enhanced facilitation of hippocampal glutamate release by the A2AR agonist, CGS21680 (30 nM), and a larger LTP amplitude (54 ± 8 % vs. 21 ± 5 % in controls) that was restored to control levels (30 ± 10 %) by the A2AR antagonist, SCH58261 (50 nM). Notably, caffeine intake reverted memory deficits and reverted the loss of hippocampal synaptic markers but did not affect helpless or anxiety behavior. These results reinforce the validity of HM as an animal model of depression by showing that they also display reference memory deficits. Furthermore, caffeine intake selectively reverted memory but not mood deficits displayed by HM, which are associated with an increased density and functional impact of hippocampal A2AR controlling synaptic glutamatergic function.
authors: CNC-Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal.
authors: Nuno J
authors: NJ
authors: Machado
authors: CNC-Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal.
authors: Ana Patrícia
authors: AP
authors: Simões
authors: CNC-Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal.
authors: Henrique B
authors: HB
authors: Silva
authors: CNC-Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal.|Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, RS, 90035-003, Brazil.
authors: Ana Paula
authors: AP
authors: Ardais
authors: CNC-Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal.
authors: Manuella P
authors: MP
authors: Kaster
authors: CNC-Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal.
authors: Pedro
authors: P
authors: Garção
authors: CNC-Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal.
authors: Diana I
authors: DI
authors: Rodrigues
authors: CNC-Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal.|Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, RS, 90035-003, Brazil.
authors: Daniela
authors: D
authors: Pochmann
authors: CNC-Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal.
authors: Ana Isabel
authors: AI
authors: Santos
authors: CNC-Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal.|Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal.
authors: Inês M
authors: IM
authors: Araújo
authors: Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, RS, 90035-003, Brazil.
authors: Lisiane O
authors: LO
authors: Porciúncula
authors: CNC-Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal.|Faculty of Life Sciences, University of Coimbra, Coimbra, Portugal.
authors: Ângelo R
authors: ÂR
authors: Tomé
authors: CNC-Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal.
authors: Attila
authors: A
authors: Köfalvi
authors: EA 4651-ABTE/ToxEMAC, Faculty of Medicine and Pharmacy, University of Rouen, Rouen, France.
authors: Jean-Marie
authors: JM
authors: Vaugeois
authors: CNC-Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal.|Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors: Paula
authors: P
authors: Agostinho
authors: CNRS UMR5292; INSERM U1028; Lyon Neuroscience Research Center, Bron, France.|Université Lyon 1, Villeurbanne, France.
authors: Malika
authors: M
authors: El Yacoubi
authors: CNC-Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal. cunharod@gmail.com.|Faculty of Medicine, University of Coimbra, Coimbra, Portugal. cunharod@gmail.com.
authors: Rodrigo A
authors: RA
authors: Cunha
authors: CNC-Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal.|Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors: Catarina A
authors: CA
authors: Gomes
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants / Q000494:pharmacology / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy / Q000378:metabolism* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy / Q000378:metabolism* / Q000523:psychology; D051379:Mice; D019964:Mood Disorders / Q000188:drug therapy / Q000378:metabolism* / Q000523:psychology; D043705:Receptor, Adenosine A2A / Q000096:biosynthesis*; D013045:Species Specificity; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D000697:Central Nervous System Stimulants; D043705:Receptor, Adenosine A2A; D002110:Caffeine; D018698:Glutamic Acid
keywords: Adenosine A2A receptors; Caffeine; Depression; Glutamate release; Memory; Synaptic plasticity