<p class="first" id="P2">Impulsivity associated with abnormal dopamine (DA) function
has been observed in several
disorders, including addiction. Choice impulsivity is the preference for small, immediate
rewards over larger rewards after a delay, caused by excessive discounting of future
rewards. Addicts have abnormally high discount rates and prefer the smaller rewards
sooner. While impulsivity has been inversely correlated with DA D2 receptor (D2R)
availability in the midbrain and striatum, it is difficult to mechanistically link
the two, due to the diverse neuroanatomical localization of D2Rs, which are found
throughout the brain, in many types of neurons and neuronal subcompartments. To determine
if ventral tegmental area (VTA) D2R hypofunction is linked to impulsivity, we knocked
down D2 receptors from the VTA, using an adeno-associated viral (AAV) vector that
delivers short hairpin RNAs (shRNA) targeted against the D2R. The D2R knockdown is
restricted to neurons whose cell bodies reside in the VTA, leaving postsynaptic D2Rs
intact in the striatum, prefrontal cortex, and other mesocorticolimbic structures.
Rats were trained in a delay-discounting task to assess impulsive choice until a stable
discounting curve was obtained, and then received bilateral VTA infusions of the D2R
shRNA or a scrambled control virus. Over the next six weeks, the discounting curve
of the VTA D2R knockdown rats shifted to the left, indicating a preference for the
smaller, immediate reward, whereas the curve for control rats remained stable and
unchanged. Together these results demonstrate that a decrease in VTA D2 receptors
enhances choice impulsivity.
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