Dose response effect of methylphenidate on ventral tegmental area neurons and animal behavior

• 89% (154/173) VTA units responded; 66% (101/154) increased their firing rate.
• 92% (48/52) VTA units responded to 0.6 mg/kg; 58% (28/48) decreased firing rate.
• 80% (48/60 VTA units responded to 2.5 mg/kg; 79% (38/48) increased firing rate.
• 95% (58/61) VTA units responded to 10.0 mg/kg; 70% (43/61) increased firing rate.
• MPD caused an increase in locomotor activity with a dose response characteristic.

Methylphenidate (MPD) is the drug of choice prescribed to treat ADHD patients. More recently, MPD is also used as a cognitive enhancement and recreationally by young adults and its therapeutic effects are not fully understood. One of the neuroanatomical sites is reported to be the ventral tegmental area (VTA). The ventral tegmental area neuronal activity was recorded from freely behaving non-anesthetized rats implanted bilaterally with semi-permanent electrodes which were recorded from a wireless telemetric system. Thirty-three animals, divided randomly into four groups, were used: saline (n = 10), 0.6 mg/kg (n = 6), 2.5 mg/kg (n = 7) and 10.0 mg/kg MPD (n = 10). MPD caused an increase in locomotor activity with a dose response characteristic; 0.6 mg/kg MPD elicited some increase in locomotion, but not significantly, while 2.5 and 10.0 mg/kg MPD elicited significant increases in behavior of 191% and 870% respectively. A total of 209 ventral tegmental area units were recorded; 100% (36/36) units showed no response to saline; 89% (154/173) of the neurons responded to MPD, with the majority 66% (101/154) showing an increase in activity. In response to 0.6 mg/kg (n = 52), the majority of units 54% (28/52) showed a decrease in activity. For both 2.5 (n = 60) and 10.0 mg/kg (n = 61), the majority of ventral tegmental area units responded with an increase in activity with 63% (38/60) and 70% (43/61) respectively. This study demonstrated that the majority of ventral tegmental area neurons respond to acute MPD in a dose response characteristic and are not related to the animal's locomotor activity.