Binge Cocaine Administration in Adolescent Rats Affects Amygdalar Gene Expression Patterns and Alters Anxiety-Related Behavior in Adulthood

Background: Administration of cocaine during adolescence alters neurotransmission and behavioral sensitization in adulthood, but the effect on the acquisition of fear memories and the development of emotion-based neuronal circuits is unknown. Methods: We examined fear learning and anxiety-related behaviors in adult male rats that were subjected to binge cocaine treatment during adolescence. We furthermore conducted gene expression analyses of the amygdala 22 hours after the last cocaine injection to identify molecular patterns that might lead to altered emotional processing. Results: Rats injected with cocaine during adolescence displayed less anxiety in adulthood than their vehicle-injected counterparts. In addition, cocaine-exposed animals were deficient in their ability to develop contextual fear responses. Cocaine administration caused transient gene expression changes in the Wnt signaling pathway, of axon guidance molecules, and of synaptic proteins, suggesting that cocaine perturbs dendritic structures and synapses in the amygdala. Phosphorylation of glycogen synthase kinase 3 beta, a kinase in the Wnt signaling pathway, was altered immediately following the binge cocaine paradigm and returned to normal levels 22 hours after the last cocaine injection. Conclusions: Cocaine exposure during adolescence leads to molecular changes in the amygdala and decreases fear learning and anxiety in adulthood.