nafadotride and Attention-Deficit-Disorder-with-Hyperactivity

Previously we demonstrated reduced D2/3 receptor availability in the ventral striatum of hyper-impulsive rats on the five-choice serial reaction time task (5-CSRTT). However, the anatomical locus of D2/3 receptor dysfunction in high impulsive (HI) rats is unknown.. In the present study, we investigated whether D2/3 receptor dysfunction in HI rats is localised to the core or shell sub-regions of the nucleus accumbens (NAcb).. Rats were selected for low (low impulsive, LI) and high impulsivity on the 5-CSRTT and implanted with guide cannulae targeting the NAcb core and shell. The D2/3 receptor agonist quinpirole was locally injected in the NAcb (0.1, 0.3 and 1 μg per infusion) and its effects investigated on the performance of LI and HI rats on the 5-CSRTT as well as spontaneous locomotor activity in an open field.. Intra-NAcb core quinpirole increased premature responding in HI rats but not in LI rats. In contrast, intra-NAcb shell quinpirole strongly increased locomotor activity in HI rats, unlike LI rats. This effect was blocked by intra-NAcb shell infusions of the D2/3 receptor antagonist nafadotride (0.03 μg). However, nafadotride was ineffective in blocking the effects of intra-NAcb core quinpirole on premature responding in HI rats.. These findings indicate that impulsivity and hyperactivity are separately regulated by core and shell sub-regions of the NAcb and that HI rats show an enhanced response to D2/3 receptor activation in these regions. These results suggest that the symptom clusters of hyperactivity and impulsivity in attention-deficit hyperactivity disorder may be neurally dissociable at the level of the NAcb.

Topics: Animals; Attention Deficit Disorder with Hyperactivity; Dopamine Agonists; Dopamine Antagonists; Dose-Response Relationship, Drug; Hyperkinesis; Impulsive Behavior; Male; Motor Activity; Naphthalenes; Nucleus Accumbens; Pyrrolidines; Quinpirole; Rats; Reaction Time; Receptors, Dopamine D2; Receptors, Dopamine D3