[Abstract Title]. - Society for Neuroscience

Authors: J. M. WANG 1 , S. B. FLAGEL 1 , J. JEDYNAK 2 , S. M. CLINTON 1 , T. E.
ROBINSON 3 , *S. J. WATSON 4 , H. AKIL 1 ;
1 Molec Behav Neurosci Inst., 2 Neurosci. Program, 3 Psychology, Univ. Michigan, Ann Arbor,
MI; 4 Univ. Michigan Sch. Med., Ann Arbor, MI
Abstract: Some individuals are able to casually use drugs without ever becoming addicted,
whereas others become hooked upon first exposure to the drug. The predisposing factors that
render some individuals susceptible to addiction and protect others from developing the disorder
remains to be determined. We have utilized a population of rats selectively bred on the basis of a
novelty-seeking trait and known to differ on a number of other behaviors relevant to addiction to
examine basal differences in neuronal morphology. High-responder (HR) bred rats are those that
exhibit increased locomotor response in a novel environment (the trait they were selected for),
greater propensity for psychomotor sensitization to cocaine, and increased acquisition of drugtaking
behavior relative to their low-responder (LR) counterparts. HR-bred rats are also more
impulsive and more aggressive compared to LR-bred rats. These two lines of rats also exhibit
differences in stress responsiveness (e.g. corticosterone levels) and in basal gene expression in
the hippocampus (e.g. glucocorticoid receptor mRNA) and striatum (dopamine D2 receptor
mRNA). Thus, we used these selectively bred rats to examine differences in basal morphology in
the hippocampus (HC) and nucleus accumbens (NAc), brain regions that have been implicated in
their behavioral traits. Brains were obtained in the “basal state” from adult HR and LR rats from
the 15 th generation of our selective breeding colony. 125 µm thick coronal sections were
collected from the prefrontal cortex, NAc and HC using a vibratome. Sections were processed
for ballistic labeling of neurons with the lipophilic dye, DiI. The dye was delivered using a “gene
gun” which allowed for rapid visualization of dendrites and dendritic spines. Images of medium
spiny neurons (MSNs) in the core of the NAc and of pyramidal neurons in the CA1 subregion of
the HC were captured using a confocal microscope and spine density was analyzed using
Neurolucida ® software. To date, we have found no significant HR/LR differences in basal spine
density of MSNs in the NAc core or on basilar branches of pyramidal neurons in the CA1
subregion of the HC. However, LR rats exhibit greater spine density on apical dendrites in the
CA1 subregion of the HC relative to HR rats. Ongoing studies are examining basal differences in
other brain regions of relevance to substance abuse. These findings are, to our knowledge, the
first report of basal differences in spine morphology associated with differences in substance
abuse vulnerability and represent an important prelude to examining the impact of drugs (e.g.
cocaine) on this morphology.
Disclosures: J.M. Wang, None; S.B. Flagel, None; J. Jedynak, None; S.M. Clinton,
None; T.E. Robinson, None; S.J. Watson , None; H. Akil, None.
Poster
239. Structural Plasticity at Synapses I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm