Ventral Tegmental Area Neuronal Activity Correlates to Animals’ Behavioral Response to Chronic Methylphenidate Recorded from Adolescent SD Male Rats

Abstract

Methylphenidate (MPD) is considered as the first-line pharmacotherapy to treat ADHD. More recently, MPD has also been used as a cognitive enhancement recreationally. Its therapeutic effects are not fully understood, nor are the long term effects of the drug on brain development. The ventral tegmental area (VTA) neuronal activity was recorded from freely behaving adolescent rats using a wireless recording system. Five groups were used: saline, 0.6, 2.5, 5.0 and 10.0 mg/kg MPD. The experiment lasted for 10 days. This study demonstrated that VTA neurons respond to MPD in a dose response characteristic and the same dose of MPD can cause both behavioral sensitization and behavioral tolerance. The neuronal unit activity was evaluated based on the animals’ behavioral activity following chronic MPD administration. The study showed that the animals’ behavioral response to different acute MPD of 0.6, 2.5 and 10.0 mg/kg doses responded in a dose response characteristics. Moreover, the same chronic dose of 0.6, 2.5, and 10.0 mg/kg MPD elicits in some animals’ behavioral sensitization and in some others behavioral tolerance. Therefore, the neuronal activity recorded from animals expressing behavioral sensitization was analyzed separately from the neuronal activity recorded from of behaviorally tolerant animals and it was found that the VTA units of the behaviorally sensitization animals responded significantly different to the drug than those VTA units recorded from animals expressing behavioral tolerance.