Acute and chronic methylphenidate modulates the neuronal activity of the caudate nucleus recorded from freely behaving rats

Abstract

Methylphenidate (MPD) is currently one of the most prescribed drug therapies for attention deficit/hyperactivity disorder (ADHD) and moreover is abused for cognitive enhancement and used for recreation by the young and adults. Methylphenidate is used for prolonged periods of time and its mechanism of action on the brain is still unknown. The main action of MPD is known to act on the motive circuit of the brain, and one of these structures is the caudate nucleus (CN). The objective of this study was to investigate the neurophysiological properties of the CN neurons in response to acute and chronic administration of MPD in freely behaving animals, previously implanted with permanent semi microelectrodes. Twenty-six rats were permanently implanted with semi microelectrodes into the CN using general anesthesia. On experimental day one (ED1) the rat was placed into the testing chamber, and neuronal activity was recorded using a wireless (telemetric) headstage device following both a saline and a 2.5 mg/kg MPD injection. From ED2 to ED6 daily injections of 2.5 mg/kg MPD were administered without recordings to induce a chronic effect of the drug, preceded by three days of washout (ED7-ED9) where no injections were given. On ED10 rats were placed back into the testing chamber, the wireless headstage device was attached to skull cap and recordings were resumed for 1 h each following both a saline and re-challenge administration of 2.5 mg/kg MPD. Sixty-seven CN neuronal recorded units from twenty-six animals with identical shape and amplitude at ED1 and ED10 were evaluated. All the 67 CN units responded to MPD administration, 70% (47/67) CN units exhibited an increase in activity following initial 2.5 mg/kg MPD administration and 30% (20/67) exhibited a decrease in neuronal activity. On ED10 all the CN units showed a significant change in their firing rate baseline compared to ED1 baseline, 52% (35/67) exhibiting an increase in their ED10 baseline activity compared to ED1 baseline activity and 48% (32/67) of the CN units at ED10 exhibited decreasing activity. All the CN units responded significantly to MPD rechallenge at ED10, 57% (38/67) of the units exhibited increased neuronal activity while 43% (29/67) exhibited decreasing neuronal activity. The results indicate that the majority of the CN units exhibited neurophysiological sensitization.