title: Caffeine protects against memory loss induced by high and non-anxiolytic dose of cannabidiol in adult zebrafish (Danio rerio).
abstract: Cannabidiol (CBD) has been investigated in a wide spectrum of clinical approaches due to its psychopharmacological properties. CBD has low affinity for cannabinoid neuroreceptors and agonistic properties to 5-HT receptors. An interaction between cannabinoid and purinergic receptor systems has been proposed. The purpose of this study is to evaluate CBD properties on memory behavioral and locomotor parameters and the effects of pre-treatment of adenosine receptor blockers on CBD impacts on memory using adult zebrafish. CBD (0.1, 0.5, 5, and 10mg/kg) was tested in the avoidance inhibitory paradigm and anxiety task. We analyzed the effect of a long-term caffeine pre-treatment (~20mg/L - four months). Also, acute block of adenosine receptors was performed in co-administration with CBD exposure in the memory assessment. CBD promoted an inverted U-shaped dose-response curve in the anxiety task; in the memory assessment, CBD in the dose of 5mg/Kg promoted the strongest effects without interfering with social and aggressive behavior. Caffeine treatment was able to prevent CBD (5mg/kg) effects on memory when CBD was given after the training session. CBD effects on memory were partially prevented by co-treatment with a specific A2A adenosine receptor antagonist when given prior to or after the training session, while CBD effects after the training session were fully prevented by adenosine A1 receptor antagonist. These results indicated that zebrafish have responses to CBD anxiolytic properties that are comparable to other animal models, and high doses changed memory retention in a way dependent on adenosine.
authors.affiliation: Laboratório de Neuroquímica e Psicofarmacologia, Departamento de Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681, Caixa Postal 1429, 90619-900 Porto Alegre, RS, Brazil.
authors.forename: Luiza Reali
authors.initials: LR
authors.lastname: Nazario
authors.affiliation: Laboratório de Neuroquímica e Psicofarmacologia, Departamento de Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681, Caixa Postal 1429, 90619-900 Porto Alegre, RS, Brazil.
authors.forename: Régis
authors.initials: R
authors.lastname: Antonioli
authors.affiliation: Laboratório de Neuroquímica e Psicofarmacologia, Departamento de Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681, Caixa Postal 1429, 90619-900 Porto Alegre, RS, Brazil.
authors.forename: Katiucia Marques
authors.initials: KM
authors.lastname: Capiotti
authors.affiliation: Departamento de Neurociências e Ciências do Comportamento, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brazil; Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Jaime Eduardo Cecílio
authors.initials: JE
authors.lastname: Hallak
authors.affiliation: Departamento de Neurociências e Ciências do Comportamento, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brazil; Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Antonio Waldo
authors.initials: AW
authors.lastname: Zuardi
authors.affiliation: Departamento de Neurociências e Ciências do Comportamento, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brazil; Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), 90035-003 Porto Alegre, RS, Brazil.
authors.forename: José Alexandre S
authors.initials: JA
authors.lastname: Crippa
authors.affiliation: Laboratório de Neuroquímica e Psicofarmacologia, Departamento de Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681, Caixa Postal 1429, 90619-900 Porto Alegre, RS, Brazil; Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Carla Denise
authors.initials: CD
authors.lastname: Bonan
authors.affiliation: Laboratório de Neuroquímica e Psicofarmacologia, Departamento de Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681, Caixa Postal 1429, 90619-900 Porto Alegre, RS, Brazil; Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), 90035-003 Porto Alegre, RS, Brazil. Electronic address: rosane.silva@pucrs.br.
authors.forename: Rosane Souza
authors.initials: RS
authors.lastname: da Silva
mesh_terms: D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology*; D002185:Cannabidiol / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology*; D009043:Motor Activity / Q000187:drug effects; D043705:Receptor, Adenosine A2A / Q000187:drug effects; D015027:Zebrafish
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D000697:Central Nervous System Stimulants; D043705:Receptor, Adenosine A2A; D002185:Cannabidiol; D002110:Caffeine
keywords: Adenosine; Anxiety; Caffeine; Cannabidiol; Memory; Zebrafish