Adenosine A_2A receptors are necessary and sufficient to trigger memory impairment in adult mice

Abstract

BACKGROUND AND PURPOSECaffeine (a non-selective adenosine receptor antagonist) prevents memory deficits in aging and Alzheimer's disease, an effect mimicked by adenosine A2A receptor, but not A1 receptor, antagonists. Hence, we investigated the effects of adenosine receptor agonists and antagonists on memory performance and scopolamine-induced memory impairment in mice. EXPERIMENTAL APPROACHWe determined whether A2A receptors are necessary for the emergence of memory impairments induced by scopolamine and whether A2A receptor activation triggers memory deficits in naïve mice, using three tests to assess short-term memory, namely the object recognition task, inhibitory avoidance and modified Y-maze. KEY RESULTSScopolamine (1.0 mg·kg , i.p.) before the training session was sufficient to trigger memory impairment in the three tests in naïve mice, and this effect was prevented by SCH 58261 (1.0 mg·kg −1 , i.p.). Furthermore, i.c.v. administration of CGS 21680 (50 nmol) also impaired recognition memory in the object recognition task. CONCLUSIONS AND IMPLICATIONSThese results show that A2A receptors are necessary and sufficient to trigger memory impairment and further suggest that A1 receptors might also be selectively engaged to control the cholinergic-driven memory impairment.

Region‐specific control of microglia by adenosine A2A receptors: uncoupling anxiety and associated cognitive deficits in female rats

“…Several studies have previously shown that A 2A R blockade prevents memory deficits associated with chronic stress or depression (Batalha et al, ; Cunha et al, ; Kaster et al, ; Machado et al, ). These studies focused on the relation between synaptic dysfunction and memory deterioration and have shown that neuronal A 2A R were both necessary and sufficient to trigger memory deficits (Li et al, ; Pagnussat et al, ; Viana da Silva et al, ). Although the blockade of A 2A R is globally accepted as a cognitive enhancer and anxiolytic, in animal models of disease, the majority of the studies were performed in males or the gender was not specified.…”

How does adenosine control neuronal dysfunction and neurodegeneration?

“…), the pharmacological activation of A 2A R in the hippocampus (Pagnussat et al . ) or cingulate cortex (Pereira et al . ) or the optical activation of the A 2A R transducing system in the hippocampus (Li et al .…”

Therapeutics of Neurotransmitters in Alzheimer’s Disease

“…Caffeine consumption, which is an A2ARs antagonist, prevented the STZ-induced memory impairment and neuronal damage [207]. Similarly, Pagnussat et al studied the effect of caffeine on A2ARs for revoking the cognitive impairments in scopolamine-induced neurodegenerative mice and found the reversal of cognitive deficits with the caffeine [208]. …”