Inhibition of ventral tegmental area projections to the nucleus accumbens shell increases premature responding in the five-choice serial reaction time task in rats

Abstract

Exaggerated impulsivity and attentional impairments are hallmarks of certain disorders of behavioural control such as attention-deficit/hyperactivity disorder (ADHD), schizophrenia and addiction. Pharmacological studies have implicated elevated dopamine (DA) levels in the nucleus accumbens shell (NAcbS) in impulsive actions. The NAcbS receives its DA input from the ventral tegmental area (VTA), and we have previously shown that optogenetic activation of VTA-NAcbS projections impaired impulse control and attention in the five-choice serial reaction time task (5-CSRTT) in rats. To better understand the role of VTA-NAcbS projections in impulsivity and attention, the present study sought to inhibit this projection using optogenetics. We demonstrate that inhibiting VTA-NAcbS efferents during the last seconds of the inter-trial interval (i.e. immediately before presentation of the instructive cue) induces exaggerated impulsive action, in the absence of changes in attentional or motivational parameters in the 5-CSRTT. Together with our earlier observations, this suggests that impulse control in the 5-CSRTT is tightly controlled by VTA-NAcbS activity, with deviations in both directions resulting in increased impulsivity.

Pramipexole restores behavioral inhibition in highly impulsive rats through a paradoxical modulation of frontostriatal networks

“…In addition, considering the functional antagonism in the control over waiting impulsivity between the NAc Shell and the NAc Core, the latter promoting impulsive action and the former inhibiting it [105][106][107][108][109], the PPXinduced decrease in the mRNA levels of both C-fos and Zif268 in the NAc Core associated with sustained C-fos expression in the Shell of HI rats suggests a PPX-induced ventral striatum-mediated normalization of impulse control at a time HI rats have re-engaged their goal-directed system. While the present results highlight the role of the NAc Core in the modulatory effects pf PPX on impulsivity, other studies have also previously demonstrated using a similar 5-CSRTT paradigm that the NAc Shell [107,108], and its innervation by the VTA [110,111] also contribute to the control of impulsivity.…”