These findings show that HD rats selected by SIP exhibit compulsive and impulsive behaviour based on measures of performance on the five-choice serial reaction time task and associated with changes in monoaminergic systems in limbic-striatal circuitry.

responsible for GABA synthesis, glutamate decarboxylase (GAD 65/67, P < 0.01), as well as the dendritic marker microtubule associated protein (MAP2, P < 0.05), and the dendritic spine marker spinophilin (P < 0.05) in the left NAcb core of HI rats compared with LI rats. There were no significant differences in any of these markers in the other brain regions investigated. We also identified a strong inverse relationship between impulsivity and the lower levels of GAD 65/67 (P < 0.01; r = -0.71) and MAP2 (P < 0.05; r = -0.66) in the left NAcb core. Finally, we investigated the effects of bilateral microinfusions of GAD 65/67 antisense into the NAcb core on the level of impulsivity in LI rats. Infusions of GAD65/67antisense in this region resulted in a robust and selective increase in impulsive responding compared to a second group of LI rats infused with a scramble sequence. These findings indicate that while the number of neurons in the NAcb core may be unaltered by variation in impulsivity, the structural integrity and density of dendritic spines, together with GABA neurotransmission, may be deficient in HI rats. Collectively, these data suggest that decreased dopamine D2/3 receptor availability in the ventral striatum of HI rats may be secondary to a reduction in the density of spines on medium spiny GABA-ergic neurons in the NAcb core.

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