Abstract
Although attentional and motor alterations in Attention Deficit Hyperactivity Disorder (ADHD) have been well characterized, less is known about how this disorder impacts goal-directed behavior. To investigate whether there is a misbalance between goal-directed and habitual behaviors in an animal model of ADHD, we tested adult [P75–P105] Spontaneously Hypertensive Rats (SHR; ADHD rat model) and Wistar–Kyoto rats (WKY), the normotensive control strain, on an instrumental conditioning paradigm with two phases: a free-operant training phase in which rats separately acquired two distinct action–outcome contingencies, and a choice test conducted in extinction prior to which one of the food outcomes was devalued through specific satiety. To assess the effects of Methylphenidate (MPH), a commonly used ADHD medication, on goal-directed behavior, we injected rats with either MPH or saline prior to the choice test. Both rat strains acquired an instrumental response, with SHR responding at greater rates over the course of training. During the choice test WKY demonstrated goal-directed behavior, responding more frequently on the lever that delivered, during training, the still-valued outcome. In contrast, SHR showed no goal-directed behavior, responding equally on both levers. However, MPH administration prior to the choice test restored goal-directed behavior in SHR, and disrupted this behavior in WKY rats. This study provides the first experimental evidence for selective impairment in goal-directed behavior in rat models of ADHD, and how MPH acts differently on SHR and WKY animals to restore or impair this behavior, respectively.
Highlights
Attention Deficit Hyperactivity Disorder (ADHD) is one of the most prevalent psychiatric disorders, which is typically diagnosed in childhood and can continue to adolescence and adulthood
The spontaneously hypertensive rat strain (SHR), a rat model bred from progenitor Wistar–Kyoto rats (WKY; Okamoto and Aoki, 1963), is the most widely accepted rodent model of ADHD (Sagvolden et al, 1993; Sagvolden, 2000; Davids et al, 2003)
All rats acquired an instrumental response; Spontaneously Hypertensive Rats (SHR) rats exhibited greater response rates across training sessions compared to WKY rats
Summary
Attention Deficit Hyperactivity Disorder (ADHD) is one of the most prevalent psychiatric disorders, which is typically diagnosed in childhood and can continue to adolescence and adulthood. The neurobiological underpinnings of ADHD are not well established; dopaminergic hypofunction is thought to play an important role in the etiology of this disorder (Hynd et al, 1993; Gill et al, 1997; Waldman et al, 1998; Russell, 2003; Bush et al, 2005; Sagvolden et al, 2005b). Consistent with this notion, ADHD symptoms are reduced in response to drugs that increase dopamine signaling, such as. MPH corrects attentional and motor impairments in SHR rats, lending further support for SHR rats as a model of human ADHD (Sagvolden et al, 2005a,b; Kantak et al, 2008)
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