[Abstract Title]. - Society for Neuroscience

Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 255.14/Y29
Topic: C.15.h. Affective disorders: Animal models
Support: NIH AWARD K02 DA22346 to SLD
Brookhaven National Laboratory Directed Research and Development Program funded
by the U.S. Department of Energy (LDRD-07-096 to FAH)
NIH GRANT R01 DA15041 to SLD
This abstract has been authored by Brookhaven Science Associates, LLC under
Contract No. DE-AC02-98CHI-886 with the U.S. Department of Energy
Title: Imaging neuronal activity in the learned helplessness model of depression using 18 FDG
microPET
Authors: *M. M. MIRRIONE 1 , D. SCHULZ 1 , S. L. DEWEY 1,2 , F. A. HENN 1,3 ;
1 Med. Dept, Brookhaven Natl. Lab., Upton, NY; 2 Psychiatry Dept., New York University, Sch.
of Med., New York, NY; 3 Psychiatry Dept., Mount Sinai Sch. of Med., New York, NY
Abstract: Neuroimaging studies in humans using 2-deoxy-2[ 18 F]fluoro-D-glucose ( 18 FDG) have
revealed unique patterns of neuronal activity in depressed patients compared to healthy controls.
These studies show complex metabolic changes in the prefrontal cortex, thalamus, limbic
system, and basal ganglia, which can be associated with expression of symptoms over many
years. Here, we use small animal positron emission tomography (microPET) to measure acute
changes in neuronal activity in vivo associated with an animal model of depression. We have
chosen the „learned helplessness‟ paradigm, which has been validated pharmacologically, but not
yet explored in depth for dysfunctional neurocircuitry. Our hypothesis was that there would be
regional differences in 18 FDG uptake between learned helpless (LH) and non-learned helpless
(NLH) wild type Sprague Dawley rats. Parallel experiments are also being conducted in
congenitally helpless (cLH) and non-helpless (cNLH) rats which have been selectively bred for
over 50 generations and differ in their susceptibility to develop learned helplessness. In our
study, subjects underwent training and testing sessions (120 inescapable or 15 escapable footshocks
respectively, at 0.4 mA with a variable duration of 5-15 s), followed 1-2 hours by an
intraperitoneal injection of 18 FDG (~2 mCi/kg) in their home cage with a 45 minute uptake
period (where radiotracer distributes through the brain/body becoming trapped in metabolically
active cells). Subjects were then anesthetized (100 mg/kg Ketamine/Xylazine), and given a 10
min static microPET scan (n = 10 LH, n = 10 NLH). Data were then processed, and quantified
with a voxel based analysis using Statistical Parametric Mapping software (SPM2). The resulting
metabolic profiles of LH and NLH subjects were directly compared. Significantly higher 18 FDG
uptake was observed in several brain regions of the LH group including the medial
thalamus/habenula, retrosplenial cortex and cerebellum. These data demonstrate the potential for
characterizing metabolic patterns of helplessness to reveal areas associated with initiating and