Adolescent methylphenidate treatment differentially alters adult impulsivity and hyperactivity in the Spontaneously Hypertensive Rat model of ADHD

Abstract

Impulsivity and hyperactivity are two facets of attention deficit/hyperactivity disorder (ADHD). Impulsivity is expressed as reduced response inhibition capacity, an executive control mechanism that prevents premature execution of an intermittently reinforced behavior. During methylphenidate treatment, impulsivity and hyperactivity are decreased in adolescents with ADHD, but there is little information concerning levels of impulsivity and hyperactivity in adulthood after adolescent methylphenidate treatment is discontinued. The current study evaluated impulsivity, hyperactivity as well as cocaine sensitization during adulthood after adolescent methylphenidate treatment was discontinued in the Spontaneously Hypertensive Rat (SHR) model of ADHD. Treatments consisted of oral methylphenidate (1.5 mg/kg) or water vehicle provided Monday-Friday from postnatal day 28–55. During adulthood, impulsivity was measured in SHR and control strains (Wistar Kyoto and Wistar rats) using differential reinforcement of low rate (DRL) schedules. Locomotor activity and cocaine sensitization were measured using the open-field assay. Adult SHR exhibited decreased efficiency of reinforcement under the DRL30 schedule and greater levels of locomotor activity and cocaine sensitization compared to control strains. Compared to vehicle, methylphenidate treatment during adolescence reduced hyperactivity in adult SHR, maintained the lower efficiency of reinforcement, and increased burst responding under DRL30. Cocaine sensitization was not altered following adolescent methylphenidate in adult SHR. In conclusion, adolescent treatment with methylphenidate followed by discontinuation in adulthood had a positive benefit by reducing hyperactivity in adult SHR rats; however, increased burst responding under DRL compared to SHR given vehicle, i.e., elevated impulsivity, constituting an adverse consequence associated with increased risk for cocaine abuse liability.

Adolescent d-amphetamine treatment in a rodent model of attention deficit/hyperactivity disorder: impact on cocaine abuse vulnerability in adulthood

“…Indeed, we found that WKY display less open field activity than SHR and WIS (Somkuwar et al 2016). However, in the current work assessing cocaine abuse vulnerability, VEH-treated WKY and WIS did not significantly differ on any measure of cocaine self-administration, with the exception of differences in cocaine intake at the post-acquisition time point and at the 0.1 mg/kg cocaine dose under the FR1 schedule.…”

“…SHR exhibit core behavioral and cognitive symptoms of ADHD, including hyperactivity, impulsivity, and inattention (Adriani et al 2003; Bayless et al 2015; Hill et al 2012; Sagvolden et al 2000; Somkuwar et al 2016). SHR also model neurobiological abnormalities observed in ADHD, including greater striatal dopamine transporter density (Roessner et al 2010; Silva et al 2014).…”

Necessity for research directed at stimulant type and treatment-onset age to access the impact of medication on drug abuse vulnerability in teenagers with ADHD

“…Compared to controls, SHR are more hyperactive (Sagvolden et al, 1992), inattentive (Jentsch, 2005; De Bruin et al, 2003), and impulsive (Hand et al, 2009; Somkuwar et al, 2016). SHR also have impaired working memory (Nakamura-Palacios et al, 1996; De Bruin et al, 2003; Kantak et al, 2008) and show behavioral flexibility and habit learning deficits (Kantak et al, 2008; Wells et al, 2010; Harvey et al, 2013; Gauthier et al, 2014; Jordan et al, 2016).…”

“…In addition, SHR were more reactive to cocaine-paired cues and took longer to extinguish cocaine-seeking responses than WKY and WIS (Jordan et al, 2014; Jordan et al, 2016). Moreover, SHR had heightened locomotor activity, cocaine sensitization, and impulsive action compared to WKY and WIS (Somkuwar et al, 2016). …”

Blockade of α2-adrenergic receptors in prelimbic cortex: impact on cocaine self-administration in adult spontaneously hypertensive rats following adolescent atomoxetine treatment

“…We used the inbred Spontaneously Hypertensive Rat (SHR) model of ADHD because this strain displays core characteristics of ADHD. Compared to controls, SHR are more hyperactive, inattentive, and impulsive (Sagvolden et al 1992; Jentsch 2005; De Bruin et al 2003; Hand et al 2009; Somkuwar et al 2016). SHR also have impaired working memory and show deficits in behavioral flexibility and habit learning (Nakamura-Palacios et al 1996; De Bruin et al 2003; Kantak et al 2008; Wells et al 2010; Harvey et al 2013; Gauthier et al 2014; Jordan et al 2016b).…”