Sandra Helinski

Fuchs, RA.1

1Washington State University College of Veterinary Medicine, Department of Integrative Physiology and Neuroscience, Pullman, Washington, USA

Environmentally-induced relapse to drug-seeking behavior is dependent on accessible long-term memories of context-response-drug associations. These memories become labile upon retrieval-induced reactivation and must be reconsolidated into long-term memory stores for continued stimulus control over drug-seeking behavior. Preclinical and clinical studies suggest that pharmacological or behavioral interference with drug memory reconsolidation may be useful for relapse prevention, and systematic treatment development depends on understanding of the neurobiological underpinnings of drug memory reconsolidation. Studies from our laboratory have explored the functional neuroanatomical, pharmacological and cellular mechanisms of cocaine memory reconsolidation in an instrumental drug relapse paradigm. These studies established that cocaine memory reconsolidation in the basolateral amygdala is functionally dependent on neural activity in the hippocampus. Protein synthesis-dependent memory restabilization occurs in the basolateral amygdala, and it is regulated by endocannabinoid receptor-mediated presynaptic mechanisms, glutamate and glucocorticoid receptor-dependent postsynaptic mechanisms, and mitogen activated protein kinase-mediated signaling events. Conversely, the dorsal hippocampus appears to support early-stage memory reconsolidation, probably by maintaining post-reactivation short-term memories, via Src family tyrosine kinase and NMDA-receptor mediated neural activity. This symposium presentation will provide an overview of these studies and consider the significance of drug memory reconsolidation in terms of drug relapse and related phenomena, including the incubation of craving during drug abstinence.