title: Aged mice receiving caffeine since adulthood show distinct patterns of anxiety-related behavior.
abstract: Caffeine is the psychostimulant most consumed worldwide. Anxiogenic effects of caffeine have been described in adult animals with controversial findings about its anxiogenic potential. Besides, the effects of caffeine on anxiety with aging are still poorly known. In this study, adult mice (6months old) started to receive caffeine (0.3 and 1.0mg/mL, drinking water) during 12-14months only in the light cycle and at weekdays. The open field (OF) and elevated plus maze (EPM) testing were used to determine the effects of caffeine on anxiety-related behavior in adult and aged mice (18-20months old). Because aging alters synaptic proteins, we also evaluated SNAP-25 (as a nerve terminals marker), GFAP (as an astrocyte marker) and adenosine A1and A2Areceptors levels in the cortex. According to the OF analysis, caffeine did not change both hypolocomotion and anxiety with aging. However, aged mice showed less anxiety behavior in the EPM, but after receiving caffeine (0.3mg/mL) during adulthood they were anxious as adult mice. While SNAP-25 and adenosine A2Areceptors increased with aging, both GFAP and adenosine A1receptors were not affected. Caffeine at moderate dose prevented the age-related increase of the SNAP-25, with no effect on adenosine A2Areceptors. The absence of effect for the highest dose suggests that tolerance to caffeine may have developed over time. Aged mice showed high responsiveness to the OF, being difficult to achieve any effect of caffeine. On the other hand this substance sustained the adult anxious behavior over time in a less stressful paradigm, and this effect was coincident with changes in the SNAP-25, suggesting the involvement of this synaptic protein in the ability of caffeine to preserve changes related to emotionality with aging.
authors.affiliation: Laboratorio de Estudos sobre o Sistema Purinérgico, Departamento de Bioquimica/ICBS, Universidade Federal do Rio Grande do Sul; Rua Ramiro Barcelos, 2600 - anexo; Porto Alegre, RS 90035-003, Brazil.
authors.forename: Paulo Henrique S
authors.initials: PH
authors.lastname: Botton
authors.affiliation: Laboratorio de Estudos sobre o Sistema Purinérgico, Departamento de Bioquimica/ICBS, Universidade Federal do Rio Grande do Sul; Rua Ramiro Barcelos, 2600 - anexo; Porto Alegre, RS 90035-003, Brazil.
authors.forename: Daniela
authors.initials: D
authors.lastname: Pochmann
authors.affiliation: Laboratorio de Estudos sobre o Sistema Purinérgico, Departamento de Bioquimica/ICBS, Universidade Federal do Rio Grande do Sul; Rua Ramiro Barcelos, 2600 - anexo; Porto Alegre, RS 90035-003, Brazil.
authors.forename: Andreia S
authors.initials: AS
authors.lastname: Rocha
authors.affiliation: Laboratorio de Estudos sobre o Sistema Purinérgico, Departamento de Bioquimica/ICBS, Universidade Federal do Rio Grande do Sul; Rua Ramiro Barcelos, 2600 - anexo; Porto Alegre, RS 90035-003, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Nunes
authors.affiliation: Laboratorio de Estudos sobre o Sistema Purinérgico, Departamento de Bioquimica/ICBS, Universidade Federal do Rio Grande do Sul; Rua Ramiro Barcelos, 2600 - anexo; Porto Alegre, RS 90035-003, Brazil.
authors.forename: Amanda S
authors.initials: AS
authors.lastname: Almeida
authors.affiliation: Laboratorio de Estudos sobre o Sistema Purinérgico, Departamento de Bioquimica/ICBS, Universidade Federal do Rio Grande do Sul; Rua Ramiro Barcelos, 2600 - anexo; Porto Alegre, RS 90035-003, Brazil.
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Marques
authors.affiliation: Laboratorio de Estudos sobre o Sistema Purinérgico, Departamento de Bioquimica/ICBS, Universidade Federal do Rio Grande do Sul; Rua Ramiro Barcelos, 2600 - anexo; Porto Alegre, RS 90035-003, Brazil. Electronic address: loporciuncula@gmail.com.
authors.forename: Lisiane O
authors.initials: LO
authors.lastname: Porciúncula
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000502:physiology / Q000523:psychology; D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000503:physiopathology; D002110:Caffeine / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D060766:Drinking Water; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D011619:Psychotropic Drugs / Q000494:pharmacology*; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism
chemical_list: D000697:Central Nervous System Stimulants; D060766:Drinking Water; D005904:Glial Fibrillary Acidic Protein; D011619:Psychotropic Drugs; D043705:Receptor, Adenosine A2A; C494209:Snap25 protein, mouse; D050825:Synaptosomal-Associated Protein 25; C528900:glial fibrillary astrocytic protein, mouse; D002110:Caffeine
keywords: Adenosine; Aging; Anxiety; Caffeine; Synaptic proteins