The influence of extracellular neuromodulators such as adenosine on neural transmission and behavior has become more evident in recent years. Despite this, only a small number of studies have examined the modulatory effects of adenosine on emotional (fear) learning and memory. Using a classical fear conditioning paradigm, we have recently found that adenosine A(1) receptor activation- selectively disrupts the acquisition of contextual fear conditioning while sparing the expression of context-elicited fear. The acquisition of fear responses to an acoustic stimulus that was paired with footshock was also unaffected by systemic administration of a selective adenosine A(1) receptor agonist There is a paucity of direct evidence, however, linking adenosine A(1) receptors in specific brain regions to fear-related learning. Thus, the goal of the proposed work is to determine the modulatory effects of adenosine acting on A(1) receptors in specific brain regions that mediate fear learning. Ten minutes prior to fear conditioning, rats will receive bilateral infusions of a selective adenosine A(1) receptor agonist or vehicle into the basolateral amygdala, dorsal hippocampus, or nucleus accumbens. Twenty-four and forty-eight hours later, rats will once again receive drug (same dose) or vehicle infusions, then behavioral fear responses will be measured 10-minutes later. One of the long-term objectives of this research is to elucidate neuromodulatory mechanisms that influence the transmission, and possibly the plasticity underlying emotional learning. This could have important implications for the development of anxiety disorders, which are believed to be the result of a malfunction in neural circuits that mediate fear learning. Some of the brain regions that we will be investigating have been implicated in various aspects of drug addiction. Adenosine A(1) receptor activation, which influences dopamine release in the brain, may modulate dopaminergic pathways underlying the learning that is associated with addiction and substance abuse.
