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Guanosine fast onset antidepressant-like effects in the olfactory bulbectomy mice model.


ABSTRACT: The treatment of major depressive disorder (MDD) is still a challenge. In the search for novel antidepressants, glutamatergic neuromodulators have been investigated as possible fast-acting antidepressants. Innovative studies suggest that the purine cycle and/or the purinergic signaling can be dysregulated in MDD, and the endogenous nucleoside guanosine has gained attention due to its extracellular effects. This study aimed to verify if guanosine produces fast-onset effects in the well-validated, reliable and sensitive olfactory bulbectomy (OBX) model of depression. The involvement of the mTOR pathway, a key target for the fast-onset effect of ketamine, was also investigated. Results show that a single i.p. injection of guanosine, or ketamine, completely reversed the OBX-induced anhedonic-like behavior 24 or 48?h post treatment, as well as the short-term recognition memory impairment 48?h post treatment. The antidepressant-like effects of guanosine and ketamine were completely abolished by rapamycin. This study shows, for the first time, that guanosine, in a way similar to ketamine, is able to elicit a fast antidepressant response in the OBX model in mice. The results support the notion that guanosine represents a new road for therapeutic improvement in MDD.

SUBMITTER: de Almeida RF 

PROVIDER: S-EPMC7242421 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Guanosine fast onset antidepressant-like effects in the olfactory bulbectomy mice model.

de Almeida Roberto Farina RF   Pocharski Camila Barbosa CB   Rodrigues Ana Lúcia S ALS   Elisabetsky Elaine E   Souza Diogo O DO  

Scientific reports 20200521 1


The treatment of major depressive disorder (MDD) is still a challenge. In the search for novel antidepressants, glutamatergic neuromodulators have been investigated as possible fast-acting antidepressants. Innovative studies suggest that the purine cycle and/or the purinergic signaling can be dysregulated in MDD, and the endogenous nucleoside guanosine has gained attention due to its extracellular effects. This study aimed to verify if guanosine produces fast-onset effects in the well-validated,  ...[more]

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