Conditioned Place Preference Responses to SB-277011-A in Dextroamphetamine Sulfate Addicted Rats. LESLEY RUSSELL (College of the Holy Cross Worcester, MA 01610) ANDREW GIFFORD (Brookhaven National Laboratory, Upton, NY, 11973)

Dextroamphetamine sulfate, a member of the amphetamine family, is a central nervous system stimulant often used to treat attention deficit disorder (ADD) and attention deficit hyperactivity disorder (ADHD) in children. Dextroamphetamine sulfate is also commonly used to treat narcolepsy. Amphetamine use causes storage vesicles in the central nervous system to release the excitatory neurotransmitters dopamine and norepinephrine. While amphetamine usage at first causes feelings of euphoria, these feelings ultimately give way to deep depression and fatigue due to the depletion of dopamine and norepinephrine stores in the mesolimbic areas of the brain. The cycle of euphoria followed by depression often leads to amphetamine addiction. While a number of neurochemical pathways are involved in creating drug addiction, the dopaminergic pathway, specifically, is associated with the reinforcement of addictive substances and behaviors. Five types of receptors exist within the dopaminergic pathway (D1-D5). Past research has shown that the D2 class of receptors, in particular the D2R receptor, is essential in creating and sustaining drug addiction. Recently, however, a substantial body of literature has accumulated pointing also to the D3R receptor as playing a vital role in drug addiction. Current research has revealed that SB-277011-A, a highly selective D3 receptor antagonist, decreases cocaine-seeking behavior, ethanol-seeking behavior, ethanol consumption, nicotine conditioning, and nicotine-triggered relapse. Using a place preference paradigm, this study examines the effects of SB-277011-A when administered to dextroamphetamine-addicted rats (i.p.) at a dose of 3 mg/kg, 10 minutes before being posited into the place preference apparatus. The data shows that rats given a 3 mg/kg injection (i.p.) of dextroamphetamine sulfate exhibited significant drug seeking behavior. Also, despite the administered dose of SB-277011-A, dextroamphetamine addicted rats continued to exhibit a considerable amphetamine place preference, suggesting that the D3 receptor does not play a large role in amphetamine seeking behavior. This project is intended to help advance the present knowledge of the role the D3R receptor plays in drug and substance addiction and abuse.

Differentiating Between Different Forms of B-Cell Chronic Lymphocytic Leukemia Using FT-IR Spectroscopy and its Clinical Relevance as a Diagnostic Tool. JEFFREY BORACK (Binghamton University Binghamton, NY 13902) LISA MILLER (Brookhaven National Laboratory, Upton, NY, 11973)

B-cell chronic lymphocytic leukemia (B-CLL) is a disease that follows two completely different clinical courses. Two forms of the disease, in which either the IgVH gene is mutated and there is low expression of ZAP-70 and CD38, or the IgVH gene is not mutated and there is higher ZAP-70 and CD38 expression, follow a benign or more aggressive clinical path respectively. Furthermore differences in transmembrane signaling through the B-cell antigen receptor exist in these subgroups and these differences have been suggested as a central explanation for the differences in biology and outcome in the disease. By using infrared spectroscopy and an automated cluster analysis tool it is hoped to determine if there may be any clinically applicable diagnostic tests that can be conducted to differentiate between different forms of B-CLL. To accomplish this, B-cells from patients have been isolated and placed on IR reflective slides. IR spectra were taken from ~300 cells/sample using a Spectrum™ Spotlight™ FT-IR microscope with an aperture size of 25 mm2 in reflection mode. The IR spectra were analyzed using OPUS 5.0 cluster analysis. Averages of each sample were taken and then clustered using vector normalization and Ward's algorithm. Results show that distinct clusters form with the highest degree of clustering around the lipid absorption region (2900-3100 cm-1). Clusters did not develop as well for protein and nucleic acid regions. It is believed that the results found in the lipid region can be attributed to differences in membrane composition and/or lipid concentration and clusters may represent patients with different transmembrane signaling properties and possibly disease progression rate, although these remain undetermined as of yet. In the future, more tests will be conducted on additional samples to try and establish a higher degree of statistical relevance between these observations and the V-gene mutation information available on the B-CLL cases.

Effects of HZE Radiation on Motor Functions of the Brain. ODIANOSEN AYEWOH (University of Maryland Eastern Shore Princess Anne, MD 21853) DR. ONARAE RICE (Brookhaven National Laboratory, Upton, NY, 11973)

The effects of cosmic radiation on the brain were studied. This was done in order to aid the National Aeronautics and Space Association (NASA) in evaluating possible brain damages to astronauts that may result from exposure to heavy ions on a three year voyage to Mars. In this study animals (rats) were irradiated at the NASA Space Radiation Lab (NSRL) with 56Fe ions in order to simulate one aspect of the effects of cosmic radiation. There were three groups of radiation doses: 0cGY, 120cGY and 240cGY. We utilized two behavioral methods: The Rotational Rod Machine (Rotorod) and Locomotive Motor Skill Monitoring Boxes (LocoMotor Boxes). Rotorod is a device with four bi-level compartments with a rotating bar in the middle, which rotates at either a fixed speed or increasing speeds, that measures motor agility and motor learning. The Locomotor boxes work on a system linked to a monitoring computer. The interior of the boxes have infra-red beams that form a grid and traverse the entire area within the box. Each time the animal moves and breaks a beam it is registered as activity. Our results showed that heavy ions, such 56Fe, contributed to the damage of the nigro-striatal dopamine pathway, which is primarily responsible for movement. Deprenyl (selegiline) , used to treat Parkinson's Disease, is an irreversible inhibitor of monoamine oxidase B, and has shown to be a neuro-protector. Our study also revealed that the 56Fe particles caused decreased locomotor activity, as well as, deficits in motor agility and motor learning. In addition, Deprenyl was shown to have a significant impact on the group of animals with the highest irradiation level on the brain.

Severity of executive impairment in depressed cocaine addicts. ROLINDA MCINTOSH (Medgar Evers College Brooklyn, NY 11203) RITA GOLDSTEIN (Brookhaven National Laboratory, Upton, NY, 11973)

Cocaine abuse continues to be a major societal problem. From recent studies conducted at Brookhaven, there has been substantial evidence that cocaine use is associated with neuropsychological impairments. The aim of this study was to examine the effect of self-reported state depression on executive functioning, including planning, shifting, cognitive interference, decision-making, and problem solving abilities in substance dependent individuals (SDI). Participants were 64 cocaine abusers (14 females and 50 males) between the ages of 20-55. They self-reported depression using the Beck Depression Inventory (BDI), a 21-item self-report instrument intended to assess the severity of symptoms of depression within the two weeks prior to and including day of testing in adolescents and adults. Subjects with BDI scores in the range of 0-15 were considered not to be depressed (N=43), and those who scored above 15 were considered depressed (N=21). As part of a larger neuropsychological battery, all subjects were administered several measures of executive functioning. These included the Stroop Task, the Wisconsin Card Sort Task (WCST), Trails Making Test (part B), the Letter-Number Sequencing Task, mazes from the Wechsler Intelligence Scale for Children (WISC), Symbol Digit Modalities Test, and the Attention Network Test conflict subscale. Reading subscale of the Wide Range Achievement Test (WRAT) and design matrix of the Wechsler Adult Intelligence Scale (WAIS) were administered for assessment of overall level of intelligence. No significant differences were found between the depressed SDI and the non-depressed SDI in any of the inspected neuropsychological tasks, as assessed by univariate t-tests. Future studies with larger sample sizes and additional specific executive functioning task, such as the Bechara's gambling task are needed to determine the importance of the relationships between state depression and executive functioning in drug addiction.

The Use of MicroPET and Autoradiography to Study Radiation Damage to the Brain. SASHEEN FERGUSON (State University of New York - Stony Brook Stony Brook, NY 11790) ONARAE RICE (Brookhaven National Laboratory, Upton, NY, 11973)

The objective of our research is to employ MicroPET imaging to evaluate the effects of irradiation with 56FE particles on the brain, and ultimately to estimate human neurological risks from HZE radiation of prolonged missions beyond the geomagnetosphere as astronauts embark on an estimated three year mission to and from Mars. In this study animals (rats) were irradiated at the NASA Space Radiation Lab (NSRL), during NSRL 4, with 56FE ions at either doses of 0cGy, 120cGy or 240cGy in order to simulate one aspect of cosmic radiation. We tested animals six and nine months post-irradiation with microPET to assess possible deterioration to the brain. The glucose analog [18F] FDG was used to measure glucose uptake, and eventually metabolic glucose rates, in various brain regions, such as the hippocampus and substantia nigra. It is hypothesized that HZE particles may cause damage to the brain, specifically the hippocampus and striatum, which may lead to numerous complications including early onset of Parkinson's disease or memory loss. Our Results showed that there was no significant damage or differences between doses at the regions of interest. We need to conduct further studies at a longer time frame post irradiation in order to assess the effects of irradiation with 56FE particles on the brain.