Intracellular Signaling Contributions to Behaviors Relevant to Nicotine Addiction

Nicotine is the primary addictive substance in tobacco, and most smokers who quit will relapse within a year. Evidence shows that cigarette craving increases over time, termed “incubation.” The purpose of these studies was to see if protracted abstinence from chronic nicotine increases rat self-administration, an animal model with good face validity for human tobacco use, and if nicotine self-administration during daily exposure/after 8+ days of abstinence is regulated by extracellular signal-regulated kinase (ERK) signaling in the nucleus accumbens (NAc) shell or anterior cingulate cortex (PFC). ERK kinase inhibitor U0126 was infused in the NAc shell or PFC of Long Evans rats immediately prior to daily self-administration sessions and following 8+ days of abstinence. U0126 in the PFC decreased responding for nicotine during daily sessions. Following 8+ days of abstinence, animals showed a robust increase in responding for nicotine, blocked by U0126 in the NAc shell, but not the PFC. Western blots revealed that nicotine treatment decreased levels of a substrate of ERK, ribosomal s6 kinase (RSK), in the NAc shell and increased it in the PFC, which occurred independent of abstinence period. In contrast, levels of RSK were increased in the NAc shell following a nicotine challenge during the abstinence period. In summary, our data show that the ERK signaling pathway plays a vital role in nicotine addiction during daily nicotine exposure and following periods of abstinence.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Pharmacology & Toxicology

Year dc:date.available

2011

Author dc:creator

• Thompson, Lauren

Contributors dc:contributor

• Darlene Brunzell

• nicotine
• incubation
• protracted abstinence
• self-administration
• ERK
• extracellular signal regulated kinase
• Medical Pharmacology
• Medical Sciences
• Medicine and Health Sciences

Statement dc:rights

• © The Author

Identifier

https://scholarscompass.vcu.edu/etd/253

OAI identifier oai:identifier

oai:scholarscompass.vcu.edu:etd-1252