Effets of different CPP cue configuration and extinction procedures on acquisition, extinction and reinstatement of cocaine-associated memories

Abstract

Addiction is a brain disease characterized by compulsive drug-seeking and taking in spite of aversive consequences, along with craving and relapse even after long periods of abstinence. Drugs of abuse induce long-lasting changes in brain function and structure, through neuroplastic mechanisms on the learning and memory system that lead to compulsive drugtaking behavior and eventually to addiction. After several drug-context associations, context re-exposure can activate those associative-memories eliciting physiological responses and drug-seeking directed behaviors. Thus, drugs of abuse induce an aberrant enhancement and consolidation of drug-related memories and its activation by context exposure promotes compulsive drug-directed behaviors. Among all the neural systems involved in the formation and consolidation of drug-related memories, the noradrenergic system seems to be a critical component. The NE responds to emotional arousal, novel stimuli or stimuli that represent a sensory challenge and require attention. Previous data suggests that the agonism of the NE system improves appetitive and aversive emotional learning. Specifically, the evidence suggests the implication of the β2-receptors in conditioned memories induced by abused drugs. The aim of these experiments is twofold; first to compare different CPP configurations and procedures on acquisition, extinction and reinstatement of cocaine-associated memories. Second, to explore the effects of the β2-AR agonist CLE, on extinction and reinstatement of cocaine-induced CPP using the most effective procedure. For the first aim, we used two different CPP apparatus configurations (one- (A1) or two- (A2) compartment). Also, we used two different extinction procedures (force- (FE) and choice- (CE) extinction). For the second goal, we used a wide range of CLE doses following a A2 apparatus configuration and a CE procedure.