Differential Roles of Dopamine D1 and D2 Receptors in the Nucleus Accumbens in Attentional Performance on the Five-Choice Serial Reaction Time Task

Abstract

Nucleus accumbens (NAC) dopamine may play a role in attentional and executive processes, as it modulates cortico-limbic inputs, including afferents from the prefrontal cortex. The present study examined the role of NAC dopamine D1 and D2 receptors in visual attentional processes and response control in rats as assessed in the five-choice serial reaction time task (5CSRT). Rats were trained to detect the location of brief (0.5 s) visual targets presented randomly in an array of five apertures to receive food reward. They were tested after bilateral infusions of a D1 receptor antagonist (SCH 23390) and agonist (SKF 38393) and a D2 receptor antagonist (sulpiride) and agonist (quinpirole) into the NAC. While intra-NAC SCH 23390 decreased accurate responding and increased response omissions, SKF 38393 improved accuracy and decreased omissions at the lowest dose (0.1 mg/side). At higher doses, SKF 38393 increased premature 'impulsive' responding. Sulpiride impaired the attentional accuracy of responding and slowed the latency to collect the earned food reward. By contrast, intra-NAC infusions of quinpirole did not significantly affect attentional accuracy, but increased perseverative responding. Optimal performance on the 5CSRT depends on both D1 and D2 receptors in the NAC, but they modulate different aspects of performance. D1 receptor agents had more selective effects on attentional accuracy while D2 receptor stimulation did not affect accuracy or premature responses, but enhanced perseverative responding. The data are discussed in terms of the different functions of NAC dopamine receptors in the processing of information from its different cortico-limbic inputs.

Impact of Serotonin (5-HT)2C Receptors On Executive Control Processes

“…2CKO mice exhibited impaired performance in the acquisition phase of the 5-CSRTT, in a manner indicative of a substantial deficit in attentional function. During performance of this task, 2CKO mice exhibited elevated extracellular dopamine levels in the NAc, a finding in accord with prior evidence that 5-HT 2C receptors suppress ascending dopaminergic pathways (Rocha et al, 2002;Abdallah et al, 2009) and that perturbations of NAc dopamine signaling can impair attention (Cole and Robbins, 1989;Pezze et al, 2007). In addition to impaired acquisition in the 5-CSRTT, 2CKO mice also displayed impaired serial reversal learning.…”

Opposing Roles for 5-HT2A and 5-HT2C Receptors in the Nucleus Accumbens on Inhibitory Response Control in the 5-Choice Serial Reaction Time Task

“…The infusion sites were located in the NAc core close to the anterior commissure, and adjacent to the NAc shell. While previous studies (Pezze et al, 2007) have shown that the observed effects are unlikely to involve diffusion of the compounds into the dorsolateral striatum, an action within the NAc shell cannot be excluded.…”

“…Similarly, SB242084 is a high affinity antagonist with more than 100 fold selectivity for 5-HT 2C -receptors relative to 5-HT 2B or 5-HT 2A receptors (Kennett et al, 1997). The cannula placements, infusion volumes and rates used were based on previous studies (Murphy et al, 2005;Pezze et al, 2007). Infusion of 0.5 ml over 1 min restricts the spread of the drug to approximately 1 mm 3 limiting the effects of the drug to the areas of interest, (Myers, 1966;Myers et al, 1971;Routtenberg, 1972).…”

“…There is considerable evidence implicating DA-ergic mechanisms in inhibitory response control (Cole and Robbins, 1989;Robbins, 2002;Winstanley et al, 2006;Pezze et al, 2007;Dalley et al, 2007). Neurochemical and behavioral studies indicate that 5-HT 2 receptor subtypes differentially modulate DA as well as noradrenaline function within the NAc (Gobert and Millan, 1999;Di Matteo et al, 2001;Porras et al, 2002;Bubar and Cunningham, 2006).…”

Hippocampal Neural Disinhibition Causes Attentional and Memory Deficits

“…In contrast, sustained attention is highly dependent on balanced prefrontal activity, with prefrontal lesions (Chudasama and Robbins 2006), functional inhibition (by the GABA-A agonist muscimol) or disinhibition ) all markedly disrupting attention on the 5CSRT test. Sustained attention on the 5CSRT test also requires an optimal level of prefrontal (Granon et al 2000) and ventral striatal (Pezze et al 2007) dopamine receptor stimulation, which may be disrupted by hippocampal neural disinhibition, given that hippocampal stimulation activates the meso-prefrontal-ventral striatal dopamine system (Mitchell et al 2000; modulation of the prefrontal cortex. Selective reductions in accuracy, without increases in omissions, have also been reported in the triple transgenic mouse model of Alzheimer's disease (Romberg et al 2011) and the pilocarpine rat model of temporal lobe epilepsy (Faure et al 2014), where the primary pathology is not within the prefrontal cortex, but in brain regions, including medial temporal lobe regions, that may modulate the prefrontal cortex.…”