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.
Highlights
The prefrontal cortex (PFC) is involved in those characteristics that distinguish humans from other animals, such as self-awareness, the capacity for complex planning, problem solving, learning and memory
We assume that the methods used had no effects on the behavior of the animals and that the data after saline injection on experimental day 1 (ED1) can be used as a control in the MPD experimental groups to evaluate the drug effects
Saline rechallenge injection at experimental day 10 (ED10) compared to activity post saline injection at ED1 or at ED10 failed to alter the PFC neuronal activity in 91% (41/45) of the units (Table 2(A), saline)
Summary
The PFC is involved in those characteristics that distinguish humans from other animals, such as self-awareness, the capacity for complex planning, problem solving, learning and memory. It is estimated that 8.7% of US children meet the criteria for ADHD diagnosis [14] With such a high rate of prescription and potential misuse and abuse of MPD by adolescents and young adults [15], it is essential to study how acute and chronic MPD treatment can affect these age groups in animal models. Experiments using FMRI have shown drastically different responses to MPD exposure between adult and adolescent rats in the PFC, nucleus accumbens, and hippocampus [23]. The objective of this experiment is to study the acute and chronic dose response characteristics of MPD on PFC neuronal activity simultaneously with animal behavior in adolescent rats and to evaluate the neuronal activity data based on animal behavioral responses. PFC units recorded from animals expressing behavioral sensitization to repetitive (chronic) MPD exposure were evaluated separately from the PFC neuronal activity recorded from animals that did not express behavioral sensitization (i.e. tolerance)
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