Abstract
Drug-associated context-induced relapse of cocaine-seeking behaviour requires the retrieval of drug-associated memory. Studies exploring the underlying neurobiological mechanism of drug memory formation will likely contribute to the development of treatments for drug addiction and the prevention of relapse. In our study, we applied a cocaine-conditioned place preference (CPP) paradigm and a self-administration paradigm (two drug-associated memory formation model) to confirm the hypothesis that the Src kinase Fyn critically regulates cocaine-associated memory formation in the hippocampus. For this experiment, we administered the Src kinase inhibitor PP2 into the bilateral hippocampus before cocaine-CPP and self-administration training, and the results showed that pharmacological manipulation of the Src kinase Fyn activity significantly attenuated the response to cocaine-paired cues in the cocaine-CPP and self-administration paradigms, indicating that hippocampal Fyn activity contributes to cocaine-associated memory formation. In addition, the regulation of cocaine-associated memory formation by Fyn depends on Tau expression, as restoring Tau to normal levels disrupted cocaine memory formation. Together, these results indicate that hippocampal Fyn activity plays a key role in the formation of cocaine-associated memory, which underlies cocaine-associated contextual stimulus-mediated regulation of cocaine-seeking behaviour, suggesting that Fyn represents a promising therapeutic target for weakening cocaine-related memory and treating cocaine addiction.
Highlights
Drug addiction is a prevalent neuropsychiatric disease that incurs high financial costs to society resulting from the potential for chronic relapse (Barry and McGinty, 2017)
Previous studies have suggested that PP2, a Src kinase Fyn inhibitor, is able to inhibit Fyn activity and alter Tau expression in individuals with Alzheimer’s disease (AD) (Chen et al, 2013; Li and Gotz, 2017)
We explored whether inhibition of Fyn activity suppresses cocaine-associated memory formation and modulates Tau expression
Summary
Drug addiction is a prevalent neuropsychiatric disease that incurs high financial costs to society resulting from the potential for chronic relapse (Barry and McGinty, 2017). Relapse prevention is a important goal for treatment. Long-lasting drug-associated memory formation is closely associated with the rewarding effects of the drug and drug exposure context (Bender and Torregrossa, 2020). Accumulating preclinical studies have suggested that exposure to drug-associated contextual stimuli may reactivate drug-associated memories, evoke craving, and promote drug relapse in drug addicts (Farrell et al, 2018). A better understanding of the underlying mechanism of drug-associated memory formation is necessary for the development of treatments.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.