Adolescent rats respond differently to methylphenidate as compared to adult rats- concomitant VTA neuronal and behavioral Recordings

Abstract

Methylphenidate (MPD) is the most widely prescribed psychostimulant used in adolescents and adults to treat attention-deficit/hyperactivity disorder (ADHD). The recreational use of MPD is becoming more prevalent because of its ability to improve cognitive enhancement. The ventral tegmental area (VTA) of the brain is highly associated with reward, cognition and addiction to drugs including psychostimulants like MPD. The VTA neuronal activity was recorded alongside the horizontal behavioral activity from freely behaving non-anesthetized rats. Four adolescent and four adult groups were treated with either saline, 0.6, 2.5 or 10.0 mg/kg MPD. In both adolescent and adult animals, the animals responded to MPD in a dose-dependent manner, such that as the dose of MPD increased, more animals and more VTA unit responded to the drug. The same doses of MPD elicited in some animals behavioral and neuronal sensitization and in other animals behavioral and neuronal tolerance. In the 0.6 and 10.0 mg/kg MPD dose groups there were significant differences between the age groups for how many animals expressed behavioral sensitization and behavioral tolerance to chronic MPD exposure. Additionally, the animal’s behavioral response to MPD by excitation or attenuation of activity did not always correlate to the VTA neuronal response, and the age group with significantly higher behavioral responses did not always correlate to the age group with significantly higher VTA neuronal responses for a given MPD dose. These findings differ from similar studies recorded from the prefrontal cortex (PFC), which exhibited behavioral responses continuously directly correlated to PFC responses for increasing MPD doses. This demonstrates that unlike other areas of the brain, there is not a direct relationship between VTA firing and behavioral activity, suggesting that there is input or modulation of this area from elsewhere in the brain. Further investigation is needed to clearly understand the relationship between VTA firing rates and behavioral responses to different MPD doses, especially given the significant differences in response between young and adult animals and the increasing use of the drug in adolescent populations.