ADENOSINE AND MEMORY STORAGE: EFFECT OF A(1) AND A(2) RECEPTOR ANTAGONISTS.

Rationale: Caffeine is a non-selective A1/A2 adenosine receptor antagonist which is known to improve cognitive performance in humans. This effect of caffeine has been attributed to its antagonism of adenosine receptors. Objective: The present study was devised to identify the role of A1 and A2A adenosine receptors in the facilitation of memory consolidation in mice performing a passive avoidance task. Methods: Adult albino Swiss male mice were used. The mice were trained in a step-through inhibitory avoidance task in which they were punished by a foot-shock (0.4 mA, 5 Hz, for 3 s) delivered through the grid floor. Caffeine (0.1, 0.3, 1.0 and 3.0 mg/kg), SCH 58261 (0.1, 0.3, 1.0 and 3.0 mg/kg) and DPCPX (0.1, 0.3, 1.0 and 3.0 mg/kg) were injected IP immediately or 180 min after training. The retention test was performed 24 h after training. Results: Caffeine and the selective A2A adenosine receptor antagonist SCH 58261 facilitated retention when administered immediately after training, but not when administered 180 min later. The dose response was a bell-shaped curve. Conversely, post-training administration of the selective A1 adenosine receptor antagonist DPCPX did not affect retention. Caffeine and SCH 58261 had no effect in mice not given the foot-shock on the training trial, a finding indicating that the drug’s effect on retention was specific. Conclusions: These results suggest that A2A but not A1 adenosine receptors are involved in memory retention and consolidation.