Adenosine and memory storage: effect of A(1) and A(2) receptor antagonists

Caffeine is a non-selective A(1)/A(2 )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.

The present study was devised to identify the role of A(1 )and A(2A) adenosine receptors in the facilitation of memory consolidation in mice performing a passive avoidance task.

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.

Caffeine and the selective A(2A) 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 A(1) 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.

These results suggest that A(2A) but not A(1) adenosine receptors are involved in memory retention and consolidation.