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, intra-NAcb 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.

Figure 1

Levels of impulsivity expressed as square root of premature responses (premature responses/total trials) on the 5-CSRT task, during baseline sessions (2–5,7–10; ITI of 5 s) and long ITI sessions (1,6,11; ITI of 7 s), in HI and LI selected for intra-shell (group: F(1,14)=161.284, p⩽0.0001; session: F(10,140)=64.581; p⩽0.0001; group × session: F(10,140)=2.440, p⩽0.001) (a) or intra-core (group: F(1,14)=54.366, p⩽0.0001; session: F(10,140)=54.658; p⩽0.0001; group × session: F(10,140)=5.203, p⩽0.0001) (b) microinfusion experiments.

Figure 2

Schematic representations of injector tips in the shell (n=11) (a) and the core (n=12) (b) of the NAcb. Reconstructed from Paxinos and Watson (1998).

Figure 3

Effects of intra-NAcb shell (diagonal stripes) or core (vertical stripes) microinfusions of nafadotride (0, 0.03, or 0.1 μg per 0.5 μl) on impulsivity in HI (a) and LI (b) rats on the 5-CSRT task. Impulsivity is expressed as square root of premature responses (premature responses/total trials). For the shell experiment, n=6 HI and n=5 LI rats. For the core experiment, n=6 HI and n=5 LI. Doses are expressed in μg/0.5 μl. Each bar represents the mean±SEM. ^*p⩽0.05.

Figure 4

Effects of intra-NAcb shell (diagonal stripes) or core (vertical stripes) microinfusions of aripiprazole (0, 0.03, 0.1, or 0.3 μg per 0.5 μl) on impulsivity in HI (a) and LI (b) rats on the 5-CSRT task. Impulsivity is expressed as square root of premature responses (premature responses/total trials). For the shell experiment, n=6 HI and n=5 LI rats. For the core experiment, n=6 HI and n=6 LI. Doses are expressed in μg/0.5 μl. Each bar represents the mean±SEM.

Figure 5

Effects of systemic nafadotride administration on 5-CSRT task performance in HI (black bars, n=7) and LI rats (gray bars, n=8). Doses are expressed in mg/kg. Each bar represents the mean±SEM. (a) Impulsivity expressed as square root of premature responses (premature responses/total trials). (b) Perseveration expressed as a number of perseverative nose pokes. (c) Choice accuracy expressed as a percentage of correct responses. (d) Omission expressed as a percentage of omissions. (e) Correct response latency expressed in sec. (f) Magazine latency expressed in seconds. ^***p⩽0.001.

Figure 6

Effects of systemic aripiprazole administration on 5-CSRT task performance in HI (black bars, n=7) and LI rats (gray bars, n=8). Doses are expressed in mg/kg. Each bar represents the mean±SEM. (a) Impulsivity expressed as square root of premature responses (premature responses/total trials). (b) Perseveration expressed as a number of perseverative nose pokes. (c) Choice accuracy expressed as a percentage of correct responses. (d) Omission expressed as a percentage of omissions. (e) Correct response latency expressed in seconds. (f) Magazine latency expressed in seconds. ^*p⩽0.05, ^**p⩽0.01, ^***p⩽0.001.