Attention-deficit hyperactivity disorder (ADHD) is a heterogeneous syndrome, which is characterized by behavioral and cognitive dysfunctions, including inattention, impulsivity and hyperactivity (Kirby et al.
2002; Krain and Castellanos
2006; Pasini et al.
2007; Goldman et al.
1998). Clinical studies have emphasized a genetic predisposition; however, more recently there is evidence that adverse environmental factors, such as chronic family conflicts, decreased family cohesion and parental psychopathology also may play a significant role (Biederman et al.
1995; Counts et al.
2005; Miller et al.
2006). The vast majority of animal models, in which the mechanisms and etiology of attention-deficit hyperactivity disorder (ADHD) are investigated experimentally, such as the spontaneously hypertensive rat (Sagvolden
2000), the dopamine transporter knockout mouse (Gainetdinov and Caron
2001), and others (Davids et al.
2003), are based on the analysis of genetic predispositions. In contrast, the contribution of environmental factors on the etiology of ADHD has been studied in much less detail. The semi-precocial rodent
Octodon degus represents an ideal animal model for the analysis of the environmental, experience-mediated influences, since degus are—similar to human babies and unlike the commonly used altricial laboratory rodents—born with functional sensory systems (open ears and eyes). Previous studies in this animal model have shown that repeated disturbance of the family environment during the first weeks of life results in behavioral dysfunctions resembling symptoms of ADHD (Braun et al.
2003). These behavioral abnormalities are paralleled by changes of dendritic spine density in prefrontal and limbic brain areas (Helmeke et al.
2001; Poeggel et al.
2003a), which can be normalized by a chronic treatment with methylphenidate (Zehle et al.
2007), a compound that is used to treat ADHD symptoms in children and adolescents.
The aim of this study was to test the hypothesis that environmental factors such as early life adversity contributes to the etiology of ADHD-like behavioral symptoms, and results in dysfunctional activation patterns in limbic and prefrontal regions. Based on previous observations that ELS significantly alters dopaminergic innervation patterns in the medial prefrontal cortex and in the nucleus accumbens (Braun et al.
2000; Gos et al.
2006; Kunzler et al.
2015) and reduces dopaminergic functions (Jezierski et al.
2007), we predicted that treatment with methylphenidate should “normalize” the ELS-induced ADHD-like behavioral and brain dysfunctions.