8-pCPT, an Epac activator, impairs conditioned place preference based on nucleus accumbens amphetamine in rats

ObjectivesDopamine receptor-mediated 3′,5′-cyclic adenosine monophosphate (cAMP)-dependent intracellular signalling is important for reward-related learning. cAMP activates cAMP-dependent protein kinase (PKA) and exchange protein directly activated by cAMP (Epac). We tested the hypothesis that reward-related learning may be mediated by Epac.MethodsWe evaluated conditioned place preference (CPP) on the basis of nucleus accumbens (NAc) injections of amphetamine (20 μg/0.5 μl/side) plus Sp-adenosine 3′,5′-cyclic monophosphorothioate triethylamanine (Sp-cAMPS) (0.1, 1.0, 10, 15, 20 μg/0.5 μl/side), an activator of both PKA and Epac, or amphetamine (20 μg) plus 8-(4-chlorophenylthio)-2′-O-methyladenosine-3′,5′-cyclic monophosphate (8-pCPT) (0.73, 1.27, 1.45, 2.89, 5.78, 11.56 μg/0.5 μl/side), an activator of Epac.ResultsIn agreement with previous results, Sp-cAMPS dose-dependently impaired CPP. 8-pCPT impaired CPP at one dose (1.45 μg/0.5 μl/side) and we replicated this effect three times.ConclusionThe results implicate Epac in the acquisition of reward-related learning.