Transcript The Influence of dFosB in the Nucleus Accumbens on Natural

The Influence of dFosB in the
Nucleus Accumbens on Natural
Reward-Related Behavior
WALLACE ET AL. 2008
BY SAMIR ZAMAN
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.
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.
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.
Delta FosB : Addiction
Drug Naive
Infusion of
dFosB to
Drug Naive
Day 1
Chronic
Cocaine
Day 10
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.
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?
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
Results
 Chronic sucrose and
sexual experience
increase both dFosB.
 Infused dFosB leads to
increased sucrose
consumption and
sexual behavior.
 Sexual experience
increases sucrose
consumption.
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.