Concomitant behavioral and prefrontal cortex neuronal responses following acute and chronic methylphenidate exposure in adolescent and adult rats

•Behavioral activity responded to MPD in a dose-dependent fashion.•MPD elicited behavioral sensitization in some animals and tolerance in others.•PFC units from sensitized animals mainly demonstrated an increase in firing rate.•PFC units from tolerant animals mainly demonstrated a decrease in firing rate.•Chronic high-dose MPD modulated baseline behavior in adolescents but not adults. There is growing concern that the psychostimulant Methylphenidate (MPD) is being abused for cognitive enhancement and recreation by healthy adults and adolescents seeking to improve their work or academic performance. This study concomitantly recorded the behavioral and prefrontal cortex (PFC) neuronal activity in freely behaving animals exposed to acute and chronic MPD doses (0.6, 2.5, and 10.0 mg/kg MPD) in order to compare MPD effects on adult and adolescent rats. The PFC is one of the primary brain areas affected by MPD and the drug of choice for treating ADHD. Moreover, the PFC is one of the last brain areas to complete development, suggesting that the behavioral and neurophysiological response to MPD may differ in adolescents and adults. In both adult and adolescent animals, it was observed that the same repetitive (chronic) dose of either 0.6, 2.5, or 10.0 mg/kg MPD elicited behavioral sensitization in some animals and tolerance in others, experimental biomarkers indicating drug of abuse symptoms, and the majority of PFC units recorded in animals expressing behavioral sensitization or tolerance to chronic MPD exposure responded by increasing and decreasing their neuronal firing rate, respectively. Further, it was shown that high doses of 10.0 mg/kg MPD significantly modified adolescent behavioral activity but did not impact adults suggesting that adolescents may be more receptive to chronic MPD exposure. These findings raise concerns regarding the use and abuse of MPD in normal, healthy individuals and support the notion that the adolescent PFC is more susceptible than the adult PFC to neuromodulation from chronic MPD use.