Poster No:
687
Submission Type:
Abstract Submission
Authors:
Milky Kohno1, Laura Dennis2, Jazryn Nagum3, tianna huss3, Alea Sonnon3, Sophia Swain3, Joyce Zafaralla3, Wesley Ng3, Wililam Hoffman2
Institutions:
1Portland VA Health Care System, Portland, OR, 2Portland VA Health Care System, PORTLAND, OR, 3Oregon Health and Science University, Portland, OR
First Author:
Co-Author(s):
tianna huss
Oregon Health and Science University
Portland, OR
Alea Sonnon
Oregon Health and Science University
Portland, OR
Sophia Swain
Oregon Health and Science University
Portland, OR
Wesley Ng
Oregon Health and Science University
Portland, OR
Introduction:
Methamphetamine (MA) exposure has long-lasting neurotoxic effects, and evidence for MA-induced neuroinflammation comes from both clinical and preclinical studies. Animal models show that MA exposure leads to morphological changes that are consistent with reactive gliosis and increases the expression of factors associated with immune response activation, including pro-inflammatory cytokines released by activated glia cells. There is strong evidence that inflammatory biomarkers target the striatum and dysregulate dopamine signaling thereby contributing to dopamine-related behavioral deficits. Recently, animal models have shown a link between markers of inflammation and brain function; such that, administration of inflammatory cytokines alters the activation of reward-related brain regions and modifies the response to hedonic reward. These findings compliment neuroimaging results from humans showing a link between inflammation and striatal dysfunction. Taken together, these studies suggest that reducing inflammation is a reasonable therapeutic target and has the potential to accelerate effective strategies for stimulant-use disorders that present with inflammatory brain markers and abnormal brain function. This randomized placebo-controlled study of ibudilast, a nonselective phosphodiesterase (PDE) inhibitor tested whether reducing inflammation improved brain function in individuals diagnosed with a methamphetamine use disorder.
Methods:
Thirteen participants with MA use disorder completed a double-blind randomized placebo-controlled trial of ibudilast. Neuroimaging measures, neurocognitive testing, and measures of drug use and craving was collected before and after the 6-week trial. Resting-state data was collected on a 3T Siemens TIM Trio. Standard preprocessing steps were applied. Seed-based analysis was performed using regions of interest of the right dorsolateral prefrontal cortex (DLPFC) and striatum. Two-way repeated measures ANOVA on parameter estimates between DLFPC and nucleus accumbens were examined in SPSS 22.
Results:
Preliminary results indiciate a significant time by treatment interaction on RSFC, where the ibudilast group show greater change in the functional connectivity between the right DLPFC and nucleus accumbens. Increases in the connectivity between the right DLPFC and striatum were correlated with reduction in MA use in the ibudilast group but not in the control group.
Conclusions:
The results suggest that ibudilast alters brain connectivity, as indicated by significant time by treatment interaction on right DLPFC to ventral striatum connectivity. The results suggest that a downregulation of inflammation may positively effect corticostriatal connectivity to reduce drug use. Although preliminary, results provide a scientific basis for additional testing of ibudilast as a potential adjunct to treatment for MA dependence and other drug-use disorders
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Physiology, Metabolism and Neurotransmission :
Pharmacology and Neurotransmission 2
Keywords:
Addictions
1|2Indicates the priority used for review
Provide references using author date format
see poster for references