Divergent effects of D2/3 receptor activation in the nucleus accumbens core and shell on impulsivity and locomotor activity in high and low impulsive rats

Abstract

RationalePreviously 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.ObjectiveIn 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).MethodsRats 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.ResultsIntra-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.ConclusionsThese 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-013-3010-3) contains supplementary material, which is available to authorized users.

Dissecting impulsivity and its relationships to drug addictions

“…Additionally, heightened anticipatory responding has been associated with low dopamine content and reduced dopamine D2‐like receptor availability in the ventral striatum . Pharmacological manipulation of D2‐like receptors affects this form of impulsivity and its modulation by amphetamine, with baseline impulsivity affecting sensitivity to D2 manipulations . Moreover, the core and shell subregions of the nucleus accumbens may exert opposing influences on the relationship between dopamine D2‐like receptors and premature responding, with D2‐like receptor antagonism increasing and decreasing impulsivity in the shell and core, respectively …”

Long‐term, calorie‐restricted intake of a high‐fat diet in rats reduces impulse control and ventral striatal D2 receptor signalling – two markers of addiction vulnerability

“…Furthermore, rats that make more premature, i.e. impulsive, responses on the five‐choice serial reaction time task (5CSRTT), a well‐established rodent analogue of clinical tests for attention and impulse control (Voon et al ., ), also express fewer D 2 Rs and D 3 dopamine receptors (D 3 Rs) in the ventral striatum, are differentially sensitive to the effects of intrastriatal infusions of dopamine receptor ligands, and self‐administer cocaine in an addiction‐like manner (Dalley et al ., ; Belin et al ., ; Besson et al ., ; Moreno et al ., ).…”

“…Furthermore, rats that make more premature, i.e. impulsive, responses on the fivechoice serial reaction time task (5CSRTT), a well-established rodent analogue of clinical tests for attention and impulse control (Voon et al, 2014), also express fewer D 2 Rs and D 3 dopamine receptors (D 3 Rs) in the ventral striatum, are differentially sensitive to the effects of intrastriatal infusions of dopamine receptor ligands, and self-administer cocaine in an addiction-like manner (Dalley et al, 2007;Belin et al, 2008;Besson et al, 2010;Moreno et al, 2013). Impulsivity and altered dopamine transmission are also observed in obesity and BED (Dawe & Loxton, 2004;Stice et al, 2008;Wang et al, 2011;Michaelides et al, 2012;Babbs et al, 2013;Schag et al, 2013), contributing to a widespread view that palatable energy-dense foods might be 'addictive'.…”

The 5-Choice Serial Reaction Time Task: A Task of Attention and Impulse Control for Rodents

“…In contrast, increasing the stimulus duration minimizes the attentional demands of the task; this can be used to determine if a manipulation interferes with the ability to execute the basic response requirements of the task 12 . Increasing the duration of the ITI can be used to determine whether a particular manipulation affects impulsive responding 1,7,8,[13][14][15] . Moreover, using test day challenges, such as those just described, can reveal deficits 10 or enhancements 16,17 of behavior that are not apparent in well trained rats tested using standard testing parameters.…”

“…The effects of task performance on neurotransmitter release 34 and metabolic activity 35 in discrete brain areas have also been assessed. In addition, performance on the task can be used to separate rats into groups based on baseline attentional performance 30,31 or levels of impulsivity 15,32 4. Begin each trial with an inter trial interval (ITI) during which only the house light is illuminated.…”