TY  - JOUR
PY  - 2014//
TI  - Gamma aminobutyric acidergic and neuronal structural markers in the nucleus accumbens core underlie trait-like impulsive behavior
JO  - Biological psychiatry
A1  - Caprioli, Daniele
A1  - Sawiak, Stephen J.
A1  - Merlo, Emiliano
A1  - Theobald, David E. H.
A1  - Spoelder, Marcia
A1  - Jupp, Bianca
A1  - Voon, Valerie
A1  - Carpenter, T. Adrian
A1  - Everitt, Barry J.
A1  - Robbins, Trevor W.
A1  - Dalley, Jeffrey W.
SP  - 115
EP  - 123
VL  - 75
IS  - 2
N2  - BACKGROUND: Pathological forms of impulsivity are manifest in a number of psychiatric disorders listed in DSM-5, including attention-deficit/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.<p />  <p>Language: en</p>
LA  - en
SN  - 0006-3223
UR  - http://dx.doi.org/10.1016/j.biopsych.2013.07.013
ID  - ref1
ER  -