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Guanosine Anxiolytic-Like Effect Involves Adenosinergic and Glutamatergic Neurotransmitter Systems.

Abstract：

:Accumulating evidences indicate that endogenous modulators of excitatory synapses in the mammalian brain are potential targets for treating neuropsychiatric disorders. Indeed, glutamatergic and adenosinergic neurotransmissions were recently highlighted as potential targets for developing innovative anxiolytic drugs. Accordingly, it has been shown that guanine-based purines are able to modulate both adenosinergic and glutamatergic systems in mammalian central nervous system. Here, we aimed to investigate the potential anxiolytic-like effects of guanosine and its effects on the adenosinergic and glutamatergic systems. Acute/systemic guanosine administration (7.5 mg/kg) induced robust anxiolytic-like effects in three classical anxiety-related paradigms (elevated plus maze, light/dark box, and round open field tasks). These guanosine effects were correlated with an enhancement of adenosine and a decrement of glutamate levels in the cerebrospinal fluid. Additionally, pre-administration of caffeine (10 mg/kg), an unspecific adenosine receptors' antagonist, completely abolished the behavioral and partially prevented the neuromodulatory effects exerted by guanosine. Although the hippocampal glutamate uptake was not modulated by guanosine (both ex vivo and in vitro protocols), the synaptosomal K+-stimulated glutamate release in vitro was decreased by guanosine (100 μM) and by the specific adenosine A1 receptor agonist, 2-chloro-N 6-cyclopentyladenosine (CCPA, 100 nM). Moreover, the specific adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 nM) fully reversed the inhibitory guanosine effect in the glutamate release. The pharmacological modulation of A2a receptors has shown no effect in any of the evaluated parameters. In summary, the guanosine anxiolytic-like effects seem closely related to the modulation of adenosinergic (A1 receptors) and glutamatergic systems.

journal_name

Mol Neurobiol

journal_title

Molecular neurobiology

authors

Almeida RF,Comasseto DD,Ramos DB,Hansel G,Zimmer ER,Loureiro SO,Ganzella M,Souza DO

doi

10.1007/s12035-015-9660-x

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

423-436

issue

1

eissn

0893-7648

issn

1559-1182

pii

10.1007/s12035-015-9660-x

journal_volume

54

pub_type

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