The Influence of dFosB in the Nucleus Accumbens on Natural Reward-Related Behavior

1. The Influence of dFosB in the Nucleus Accumbens on Natural Reward-Related Behavior Wallace et Al. 2008 By Samir Zaman

2. Nucleus Accumbens (NAc) • aka Ventral Straitum • Part of the mesolimbic pathway • Receives input: Ventral Tegmental Area • Sends: Prefrontal Cortex It is a key region of interest in the study of drug addiction and depression because of its key role in mediating reward.

3. Delta FosB (dFosB): Structure Weeeeee! • Fos proteins, derived from the FosB gene, heterodimerize with Jun family proteins to form Activator Protein-1 transcription factors. • Delta FosB is a truncated version of the FosB protein, and is a much more stable isoform. dFosB is a long-lasting isoform of the FosB protein and can form AP-1 that can persist long after their production.

4. Delta FosB: Role in Addiction • Addiction not only a psychosis - there is a profound change in brain chemistry that makes it so hard to overcome. • Growing body of evidence pointing to dFosB as a key player in mediating the lifelong biolgical changes in addiction due to its stability and role mediating reward.

5. Delta FosB : Addiction Drug Naive Infusion of dFosB to Drug Naive Day 10 Day 1 Chronic Cocaine

6. Natural Reward • In addiction to mediating addiction, the NAc has been shown to play a role in regulating responses to natural rewards. • Mouse wheel running has been shown to increase levels of dFosB. • Mice infused with dFosB run more. Though more infrequently studied, dFosB plays as great a role in mediating natural rewards as drug-related rewards.

7. The Experiment • Noticing these trends with dFosB in the NAc in regards to natural rewards, they wanted to see how one naturally rewarding situation can modulate the sensation of reward to other rewarding situations. ...Affect... Does this… …this?

8. Methods • Two experiments: Measuring dFosB and sucrose consumption in two-bottle test after mice were given sucrose solutions or were sexually experienced. • Western Blotting Assay – punches are taken of the NAc and antibodies are used to stain proteins. Useful for comparing levels protein in a given region. • Immunohistochemistry – Use of antibodies to tag proteins of interest in a section of fixed brain tissue to be examined under a microscope. • Viral infusion of dFosB – stereotaxic surgery was done on mice and a viral vector coding for dFosB was directly infused into the NAc

9. Results • Chronic sucrose and sexual experience increase both dFosB. • Infused dFosB leads to increased sucrose consumption and sexual behavior. • Sexual experience increases sucrose consumption.

10. Implications and Takeaway • The results of this study show that dFosB, which has such an important role in the study of addiction, is also a key component in mediating reward from natural sources. • A chronic source of one reward can enhance sensitivity to the rewarding effects of another source. • In terms of drug abuse, it is a possible mechanism whereby the ‘gateway effect’ can manifest itself.