Examining the role of E3 Ubiquitin ligase Smurf1 during withdrawal following cocaine self-administration

Drug addiction is a disease characterized by episodes of relapse despite periods of drug abstinence. The ubiquitin-proteasome system (UPS) degrades proteins and is involved in cocaine-induced plasticity in the nucleus accumbens (NAc); however, E3 ubiquitin ligases (E3s), which conjugates ubiquitin to substrates for proteasomal degradation, have not been studied following cocaine exposure. Here we examined E3 Smad ubiquitinylation regulatory factor-1 (Smurf1) and found that following cocaine self-administration, Smurf1 was decreased, while substrates ras homolog gene family, member A (RhoA) and Smad1/5 were increased, in the NAc in a withdrawal dependent manner. Furthermore, viral-mediated manipulation of Smurf1 bi-directionally mediated cue-induced cocaine seeking but did not affect food seeking or locomotor activity. Finally, Smad1/5-associated transcription factor Runt-related transcript factor 2 (Runx2) was also increased during withdrawal and binding on genes that regulate cocaine plasticity was enhanced. Together, this study demonstrates that Smurf1 mediates relapse behaviour by governing cocaine plasticity during withdrawal following self-administration.

Grantor dc:publisher

State University of New York at Buffalo

Year dc:date.issued

2018

Author dc:creator

• Viswanathan, Rathipriya

Contributors dc:contributor

• Dietz, David
• Neuroscience

• neurosciences
• behavioral sciences
• pharmacology

Statement dc:rights

• Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.
• Copyright retained by author.

Language dc:language

eng

Handle dc:identifier

http://hdl.handle.net/10477/77927

OAI record oai:identifier

https://ubir.buffalo.edu/oai/request?verb=GetRecord&metadataPrefix=qdc&identifier=oai%3Aubir.buffalo.edu%3A10477%2F77927