Adenosine A1 receptor activation selectively impairs the acquisition of contextual fear conditioning in rats

Three experiments were conducted to examine the importance of adenosine A1 receptors for the acquisition and expression of hippocampal-dependent and hippocampal-independent forms of conditioned fear. In Experiment 1, the selective adenosine A1 receptor agonist, N6-cyclopentyladenosine (CPA), or saline was administered intraperitoneally to male rats 30 min prior to Pavlovian fear conditioning, which consisted of 7 tone-shock pairings. Adenosine A1 receptor activation dose-dependently and selectively disrupted the acquisition of contextual fear conditioning while sparing tone-shock associations. Experiments 2 and 3 demonstrated that CPA's selective disruption of contextual learning could not be attributed to context being weaker than tone conditioning or to state-dependent learning. Adenosine A1 receptor activation also impaired the expression of both context- and tone-elicited fear. These results suggest that endogenous adenosine modulates the acquisition and expression of emotional (fear) memories by acting on A1 receptors in brain regions underlying fear conditioning.