Dissociable Control of Impulsivity in Rats by Dopamine D2/3 Receptors in the Core and Shell Subregions of the Nucleus Accumbens

Abstract

Previous research has identified the nucleus accumbens (NAcb) as an important brain region underlying inter-individual variation in impulsive behavior. Such variation has been linked to decreased dopamine (DA) D2/3 receptor availability in the ventral striatum of rats exhibiting spontaneously high levels of impulsivity on a 5-choice serial reaction time (5-CSRT) test of sustained visual attention. This study investigated the involvement of DA D2/3 receptors in the NAcb core (NAcbC) and the NAcb shell (NAcbS) in impulsivity. We investigated the effects of a DA D2/3 receptor antagonist (nafadotride) and a DA D2/3 partial agonist (aripiprazole) infused directly into either the NAcbC or NAcbS of rats selected for high (HI) and low (LI) impulsivity on the 5-CSRT task. Nafadotride increased significantly the level of impulsivity when infused into the NAcbS, but decreased impulsivity when infused into the NAcbC of HI rats. By contrast, intraNAcb microinfusions of aripiprazole did not affect impulsivity. Systemic administration of nafadotride had no effect on impulsive behavior but increased the number of omissions and correct response latencies, whereas systemic injections of aripiprazole decreased impulsive and perseverative behavior, and increased the number of omissions and correct response latencies. These findings indicate an opponent modulation of impulsive behavior by DA D2/3 receptors in the NAcbS and NAcbC. Such divergent roles may have relevance for the etiology and treatment of clinical disorders of behavioral control, including attention-deficit hyperactivity disorder and drug addiction.

Modulation of impulsivity and reward sensitivity in intertemporal choice by striatal and midbrain dopamine synthesis in healthy adults

“…This idea is supported from evidence in rodents that DA in the core and shell regions of the nAc have distinct functions. Specifically, DA D 2 receptor blockade in the core and shell have opposing effects on impulsivity, with increasing impulsivity consequent to core blockade and decreasing impulsivity with shell blockade (Besson et al 2010). Likewise, DA release in the nAc shell scales with reward magnitude (Beyene et al 2010), and inactivating the nAc shell decreases preference for larger vs. smaller rewards (Stopper and Floresco 2011).…”

Adolescent Risk Taking, Cocaine Self-Administration, and Striatal Dopamine Signaling

“…Moreover, D2 mRNA is selectively lower in the accumbens shell of high impulsive compared with low impulsive rats (Besson et al, 2013), and blockade of D2/3 receptors in the accumbens shell increases impulsive action in the fivechoice serial reaction time task (whereas blockade of D2/3 receptors in the accumbens core has the opposite effect; Besson et al, 2010). These data provide functional support for the association between low striatal D2 receptor expression and elevated risk taking, and implicate the accumbens shell as an important site of action for mediating the effects of D2/3 agonists on risk taking.…”

“…Although initiation does not necessarily lead to chronic use, in cases in which this does occur, cocaine use would be expected to cause further elevations in risk taking, which could in turn promote further drug use and other maladaptive behaviors. To our knowledge, this combination of adolescent development, bi-directional relationships between an addiction-associated phenotype and drug intake, and a signature neurobiological feature of addiction (reduced striatal D2 receptors) is unique among animal models linking addiction-associated traits and drug use (Belin et al, 2008;Besson et al, 2010;Dalley et al, 2007;Robinson, 2010, 2011). In particular, because predispositions for drug use can be evident in human adolescence (Chambers et al, 2003;Chartier et al, 2010), the ability to capture a predictive phenotype at this stage of development is important for modeling vulnerability to drug use.…”

The Roles of Dopamine and Serotonin in Decision Making: Evidence from Pharmacological Experiments in Humans

“…Clinical evidence suggests that chronic substance misusers show significant impairments in the capacity to decide between probabilistic outcomes, reflecting possible disturbances of dopaminergic, and possibly serotonergic, modulation of fronto-striatal systems Paulus et al, 2003;Rogers et al, 1999b). Equally though, such deficits may reflect preexisting disturbances including, for example, elevations of D 2 receptor expression within the nucleus accumbens that promote the heightened impulsivity associated with drug-seeking behavior and, presumably, variability in decision-making function (Besson et al, 2010;Dalley et al, 2007;Jentsch and Taylor, 1999;Jentsch et al, 2002).…”