Guanosine as a promising target for fast-acting antidepressant responses

Although the rapid-onset and sustained antidepressant responses elicited by ketamine have gained considerable attention in recent years, it has some knock-on effects that limit its widespread clinical use. Therefore, ketamine is considered the prototype for the new generation of glutamate-based rapid-acting antidepressants. Within this context, it has been demonstrated that guanosine, an endogenous guanine-based purine, has overlapping mechanisms of action with ketamine and is effective in eliciting fast antidepressant-like responses and even potentiating ketamine's actions in preclinical studies. Here, we review the recent findings regarding the ability of guanosine to produce rapid-acting antidepressant-like effects and we provide an overview of the molecular mechanisms underlying its antidepressant-like actions. Moreover, the neurobiological mechanisms underpinning the ability of guanosine in boosting the antidepressant-like and pro-synaptogenic effects elicited by ketamine are also reported. Taken together, this review opens perspectives for the use of guanosine alone or in combination with ketamine for the management of treatment-resistant depression.

Automated summary

This article reviews the recent findings on the ability of guanosine to produce rapid-acting antidepressant-like effects and provides an overview of the molecular mechanisms underlying its antidepressant actions. The neurobiological mechanisms underlying guanosine's ability to enhance the antidepressant effects elicited by ketamine are also discussed. This review opens new perspectives for the use of guanosine alone or in combination with ketamine for the management of treatment-resistant depression.