Ventral Tegmental Area Neuronal Responses to Methylphenidate Correlated to Behavioral Responses of Adolescent and Adult Rats

Methylphenidate (MPD) is a psychostimulant used in the treat treatment of attention deficit hyperactivity disorder and more recently is being used as a cognitive enhancement and recreational drug. Its therapeutic effects are not fully understood, nor are the long term effects of the drug on brain development. The ventral tegmental area (VTA) is a site of psychostimulant action thought to be involved in behavioral sensitization. The aim of the this study was to first determine if there are differences in neuronal responses between individuals, with respect to neuronal firing patterns in the ventral tegmental area (VTA), and whether these differences are responsible for the conflicting reports on behavioral responses with chronic MPD exposure. Additionally, we wanted to determine if the same dose of MPD can cause both behavioral sensitization and behavioral tolerance and to examine if there are intrinsic differences in the VTA neuronal activity between the behaviorally sensitized and tolerant animals. One hundred and thirteen adolescent animals and 51 adult rats were divided into 4 groups: saline, 0.6, 2.5, and 10.0 mg/kg MPD and had their neuronal and behavioral activity recorded concomitantly following one of the chosen MPD doses. In order to determine if there are neuronal differences between these two groups the VTA neuronal activity was evaluated based on the animals’ behavioral response to chronic MPD exposure. In conclusion, acute MPD exposure elicits dose related increases in behavioral activity and following chronic MPD exposure, it was shown that the same repetitive MPD dose can elicit either behavioral sensitization or tolerance in both adolescent and adult animals. Differences were observed between the adolescent and adult for both the neuronal and behavioral data for each dose of MPD tested.