Ritalin Dose Response Effect on Medial Prefrontal Cortex and on Animal Behavior

Abstract

The prefrontal cortex (PFC) is involved in complex planning, learning, memory, attention and integrates sensory information. It was reported that the PFC was dysfunctional in attention deficit hyperactivity disorder (ADHD). Methylphenidate (MPD), a drug often prescribed for the treatment of ADHD, has potential for abuse and misuse. Most MPD studies were completed in adult subjects; however, most users were adolescents. The objective of this study was to investigate the acute and chronic dose response characteristics of MPD on PFC neuronal activity recorded in freely behaving adolescent rats. Four groups of animals were used: saline (control), 0.6, 2.5, and 10 mg/kg MPD. Acute MPD elicited a dose response increase in animals’ locomotor activity. Rechallenge with MPD at experimental day (ED10) when compared to the effect of MPD at ED1 showed no significant differences. When the animals were divided into two groups based on their individual responses to chronic MPD exposure, some animals expressed behavioral tolerance and some expressed behavioral sensitization. Electrophysiologically, a dose response characteristic for acute and chronic MPD exposure was observed. With increasing MPD doses, more PFC units responded by changing their firing rate. Moreover, the neuronal responses to chronic MPD recorded from animals expressing behavioral tolerance were significantly different compared to the neuronal population responses recorded from animals expressing behavioral sensitization. The majority of the PFC units recorded from animals expressing behavioral tolerance responded to MPD predominately by decreasing their firing rates, whereas PFC units recorded from behaviorally sensitized animals mainly showed an increase in their firing rates.