N6-cyclopentyladenosine impairs passive avoidance retention by selective action at A1 receptors

The effects of N6-cyclopentyladenosine (CPA), a highly selective agonist for adenosine A1 receptors, on retention of one-trial inhibitory avoidance behavior were examined in mice. Water-deprived animals were trained to avoid drinking by pairing foot-shock with licks from a water spout. Retention was measured as the suppression of drinking (latency to drink) 48 h following training. Administration of CPA (0.15-2.25 mumol/kg) 30 min prior to training produced a dose-dependent impairment in memory of the original avoidance task. The CPA-elicited deficits in retention performance were blocked by pretreatment with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective A1 receptor antagonist; DPCPX (15 mumol/kg) administration alone had no effect on retention performance. These findings suggest that selective activation of a presumably central population of A1 receptors may impair retention performance and influence information processing.