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Gamma Aminobutyric Acidergic and Neuronal Structural Markers in the Nucleus Accumbens Core Underlie Trait-like Impulsive Behavior

By D. Caprioli, S.J. Sawiak, E. Merlo, D.E.H. Theobald, M. Spoelder, B. Jupp, V. Voon, T.A. Carpenter, B.J. Everitt, T.W. Robbins and J.W. Dalley

Abstract

Background: Pathological forms of impulsivity are manifest in a number of psychiatric disorders listed in DSM-5, including attentiondeficit/ hyperactivity disorder and substance use disorder. However, the molecular and cellular substrates of impulsivity are poorly understood. Here, we investigated a specific form of motor impulsivity in rats, namely premature responding, on a five-choice serial reaction time task. Methods: We used in vivo voxel-based magnetic resonance imaging and ex vivo Western blot analyses to investigate putative structural, neuronal, and glial protein markers in low-impulsive (LI) and high-impulsive rats. We also investigated whether messenger RNA interference targeting glutamate decarboxylase 65/67 (GAD65/67) gene expression in the nucleus accumbens core (NAcbC) is sufficient to increase impulsivity in LI rats. Results: We identified structural and molecular abnormalities in the NAcbC associated with motor impulsivity in rats. We report a reduction in gray matter density in the left NAcbC of high-impulsive rats, with corresponding reductions in this region of glutamate decarboxylase (GAD65/67) and markers of dendritic spines and microtubules. We further demonstrate that the experimental reduction of de novo of GAD65/67 expression bilaterally in the NAcbC is sufficient to increase impulsivity in LI rats. Conclusions: These results reveal a novel mechanism of impulsivity in rats involving gamma aminobutyric acidergic and structural abnormalities in the NAcbC with potential relevance to the etiology and treatment of attention-deficit/hyperactivity disorder and related disorders

Topics: Attention-deficit/hyperactivity disorder, GABA, impulsivity, magnetic resonance imaging, nucleus accumbens, psychostimulants
Year: 2014
OAI identifier: oai:dspace.library.uu.nl:1874/313965
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