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Long-Term Effects of Chronic Oral Ritalin Administration on Cognitive and Neural Development in Adolescent Wistar Kyoto Rats
Department of Psychology, Macquarie University, Sydney 2109, Australia
The Australian School of Advanced Medicine, Macquarie University, Sydney 2109, Australia
* Author to whom correspondence should be addressed.
Received: 3 July 2012; in revised form: 24 August 2012 / Accepted: 28 August 2012 / Published: 12 September 2012
Abstract: The diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) often results in chronic treatment with psychostimulants such as methylphenidate (MPH, Ritalin®). With increases in misdiagnosis of ADHD, children may be inappropriately exposed to chronic psychostimulant treatment during development. The aim of this study was to assess the effect of chronic Ritalin treatment on cognitive and neural development in misdiagnosed “normal” (Wistar Kyoto, WKY) rats and in Spontaneously Hypertensive Rats (SHR), a model of ADHD. Adolescent male animals were treated for four weeks with oral Ritalin® (2 × 2 mg/kg/day) or distilled water (dH2O). The effect of chronic treatment on delayed reinforcement tasks (DRT) and tyrosine hydroxylase immunoreactivity (TH-ir) in the prefrontal cortex was assessed. Two weeks following chronic treatment, WKY rats previously exposed to MPH chose the delayed reinforcer significantly less than the dH2O treated controls in both the DRT and extinction task. MPH treatment did not significantly alter cognitive performance in the SHR. TH-ir in the infralimbic cortex was significantly altered by age and behavioural experience in WKY and SHR, however this effect was not evident in WKY rats treated with MPH. These results suggest that chronic treatment with MPH throughout adolescence in “normal” WKY rats increased impulsive choice and altered catecholamine development when compared to vehicle controls.
Keywords: methylphenidate; adolescent; tyrosine hydroxylase; chronic administration; prefrontal cortex; impulsivity; impulsive choice
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Pardey, M.C.; Kumar, N.N.; Goodchild, A.K.; Clemens, K.J.; Homewood, J.; Cornish, J.L. Long-Term Effects of Chronic Oral Ritalin Administration on Cognitive and Neural Development in Adolescent Wistar Kyoto Rats. Brain Sci. 2012, 2, 375-404.
Pardey MC, Kumar NN, Goodchild AK, Clemens KJ, Homewood J, Cornish JL. Long-Term Effects of Chronic Oral Ritalin Administration on Cognitive and Neural Development in Adolescent Wistar Kyoto Rats. Brain Sciences. 2012; 2(3):375-404.
Pardey, Margery C.; Kumar, Natasha N.; Goodchild, Ann K.; Clemens, Kelly J.; Homewood, Judi; Cornish, Jennifer L. 2012. "Long-Term Effects of Chronic Oral Ritalin Administration on Cognitive and Neural Development in Adolescent Wistar Kyoto Rats." Brain Sci. 2, no. 3: 375-404.