[Abstract Title]. - Society for Neuroscience

Abstract: Neuroadaptations are widely viewed as a basis for the enduring propensity to relapse
that persists during long periods following extinguished psychostimulant drug seeking or
enforced abstention from it. Investigation of such neuroadaptations has long centered on the
meso-accumbens-prefrontocortical axis, such that less is known about possible neuroadaptations
in much of the rest of the brain. Inasmuch as psychostimulant-elicited expression of the
immediate-early gene, c-fos, is commonly a starting point for neuroadaptation, we sought to have
a fresh look at Fos, the c-fos protein product, in a broad variety of brain structures, including
some that have been the object of previous attention and are known to neuroadapt. Standard
immunohistochemistry and computer-assisted counting was used to evaluate the density of Fos
neurons in several groups of rats: [1] vehicle (n=6) and [2] cocaine (n=6) self-administering for a
1 hour session; [3] vehicle (n=8) and [4] cocaine (n=9) self-administering for 6 daily 1 h
sessions; [5] investigator administered-cocaine for 6 daily sessions (n=8); [6] saline (n=6) and
[7] cocaine (n=4) self-administering for 5 daily 1 h sessions, sacked on day 6. To date groups 1-
5, have been evaluated in 15 structures. The most common profile observed, Fos expression
enhanced in all cocaine groups relative to similar saline groups, was observed in the lateral
septum, lateral part of the lateral habenula (LHb), and several basal ganglia structures, including
ventral pallidum, caudate-putamen, globus pallidus, substantia nigra reticulata and subthalamic
nucleus. In several accumbens subterritories, Fos was weakly enhanced relative to the vehicle
control after 1 session, but not after 6 sessions. Indeed, cocaine-elicited Fos was suppressed in
the caudomedial accumbens shell relative to the vehicle control after six sessions. In the anterior
cingulate cortex and medial part of the LHb, cocaine produced enhanced Fos in the 1 day self-
and 6 day investigator-administered, but not in the 6 day self-administered group. While
counting remains to be completed in numerous structures, the existing data indicate that distinct
profiles of cocaine-elicited Fos expression characterize different brain structures and may have
differing implications vis a vis neuroadaptation. Furthermore, subjective impressions in the day 6
cocaine-omitted group, still to be verified by counts, indicate that baseline Fos expression is
suppressed in some structures between self-administration sessions in the repeated cocaine selfadministration
group (group 7) relative to its control (group 6). Data for all groups will be
completed in 32 structures by meeting time.
Disclosures: M. Marinelli , USPHS NIH DA-020645, B. Research Grant (principal
investigator, collaborator or consultant and pending grants as well as grants already
received); M.L. Becker, None; A.J. Freiman, None; S. Geisler, None; D.S. Zahm, USPHS
NIH NS-23805, B. Research Grant (principal investigator, collaborator or consultant and
pending grants as well as grants already received).
Poster
274. Basal Ganglia: Transmitters and Neuromodulation II
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 274.1/II26