mental-health-2017-scientifictracks-abstracts

16 / 32

Page 42
Notes:
conferenceseries.com
Volume 19, Issue 2 (Suppl) Int J Emerg Ment Health, an open access journal
ISSN: 1522-4821 Mental Health 2017
June 21-23, 2017
Mental Health and Human Resilience
June 21-23, 2017 London, UK
3rd International Conference on
Neural mechanisms of behavioral inflexibility in psychostimulant addiction: Markers of vulnerability and
compulsive symptoms
Peter Zhukovsky
University of Cambridge, UK
Statement of the Problem: Behavioral flexibility is at the core of many disorders of compulsivity, including substance use disorder
(SUD), obsessive-compulsive disorder (OCD) and schizophrenia. Inflexible behavior has been found to be at the core of these
disorders; yet the precise neural changes underpinning the behavioral impairments remain to be clarified. In addition, inflexibility
could predispose to development of the disorder rather than arise as a consequence of it. We previously found that diminished
serotonergic signaling is crucial to inflexible, perseverative behavior. The current objectives include testing the hypothesis that trait-
like variation in behavioral flexibility predicts SUD and exploring the neural mechanisms of compulsivity.
Methodology & Theoretical Orientation: Using rat models of human behavior, a carefully controlled study featuring baseline
flexibility and anxiety assays, a long-access cocaine self-administration period and further flexibility assays was conducted. Neural
changes in receptor availability, inflammatory markers and neurotransmitter availability were examined ex vivo using receptor
autoradiography, qRT-PCRs and HPLC. Further, blood samples were analyzed for monoamine content and major serotonergic
gene expression. Blood and brain biomarkers were linked to explore the translational role of blood serotonergic and dopaminergic
measures in identifying addiction vulnerability.
Findings: The neural substrates of compulsive behavior include different aspects of serotonergic circuits, including monoamine
oxidase (MAO) activity, serotonin receptor availability and metabolism in prefrontal areas (OFC, mPFC), the striatum and dorsal
raphe nuclei of the brainstem. Trait-like variation in compulsive behavior and anxiety has been found to predict subsequent escalation
of drug taking along with impulsivity and other traits that were identified previously. Further, self-administration of cocaine resulted
in differential changes in neuroinflammatory signals in prefrontal and striatal regions and was related to the changes in dopaminergic
and serotonergic receptor binding.
Conclusion & Significance: Identifying a predisposition to lose control over drug taking and seeking is crucial to developing
interventions that help prevent substance abuse in the first place. Various personality traits, including impulsivity, anxiety and novelty
seeking have been found to predict aspects of SUD and clarifying the neural substrates of these traits alongside their correlates in
blood could prove vital to translational research seeking to identify the same vulnerabilities in humans.
Biography
Peter Zhukovsky specializes in neurobiology of compulsive disorders, with a focus on rodent models of psychostimulant addiction. His aims are two fold; firstly, to
help identify vulnerability for drug abuse and thus help prevent it and secondly, to elucidate its key neural mechanisms to help find treatments, both pharmacological
and behavioral. Using a recently developed rodent task measuring an aspect of cognitive flexibility, he combines a longitudinal approach with an ecologically valid
self-administration paradigm to elucidate neural mechanisms of psycho stimulant addiction.
Peter Zhukovsky, Int J Emerg Ment Health 2017, 19:2(Suppl)
DOI: 10.4172/1522-4821-C1-008