Abstract
Aside from its clinical symptoms of inattention, impulsivity and hyperactivity, patients with Attention/Deficit-Hyperactivity Disorder (ADHD) display reward and motivational impairments. These impairments may reflect a deficit in action control, that is, an inability to flexibly adapt behavior to changing consequences. We previously showed that spontaneously hypertensive rats (SHR), an inbred rodent model of ADHD, show impairments in goal-directed action control, and instead are predominated by habits. In this study, we examined the effects of specific dopamine receptor sub-type (D1 and D2) agonists and antagonists on goal-directed behavior in SHR and the normotensive inbred control strain Wistar-Kyoto (WKY) rats. Rats acquired an instrumental response for different-flavored food rewards. A selective-satiety outcome devaluation procedure followed by a choice test in extinction revealed outcome-insensitive habitual behavior in SHR rats. Outcome-sensitive goal-directed behavior was restored in SHR rats following injection prior to the choice test of the dopamine D2 receptor agonist Quinpirole or dopamine D1 receptor antagonist SCH23390, whereas WKY rats showed habitual responding following exposure to these drugs. This novel finding indicates that the core behavioral deficit in ADHD might not be a consequence of dopamine hypofunction, but rather is due to a misbalance between activation of dopamine D1 and D2 receptor pathways that govern action control.
Highlights
Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most prevalent psychiatric disorders, characterized by developmentally inappropriate symptoms of inattention, hyperactivity and impulsivity (Castellanos and Tannock, 2002; Barkley, 2005)
In our previous study (Natsheh and Shiflett, 2015), we found that spontaneously hypertensive rats (SHR), a rat model of ADHD, show a deficiency in goal-directed behavior that is restored by methylphenidate, which increases dopamine signaling
Our results reveal novel roles for dopamine receptor sub-types on goal-directed behavior in rats, and suggest how dysregulation of activity across these sub-types may give rise to behavioral impairments in SHR rats
Summary
Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most prevalent psychiatric disorders, characterized by developmentally inappropriate symptoms of inattention, hyperactivity and impulsivity (Castellanos and Tannock, 2002; Barkley, 2005) Along with these symptoms, individuals with ADHD show motivational impairments (Carlson and Tamm, 2000; Konrad et al, 2000; Slusarek et al, 2001; Castellanos and Tannock, 2002; McInerney and Kerns, 2003; Tripp and Wickens, 2008; Luman et al, 2010). Reduced task motivation in ADHD could reflect blunted reward sensitivity, a failure to encode action-reward contingencies, or impaired action control. Goal-directed and habitual systems place different demands on attentional resources (Hitchcott et al, 2007; Le Pelley et al, 2013; Savalia et al, 2016; Luque et al, 2017), and as a consequence individuals with ADHD may be biased toward habitual action control
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