Methylphenidate induces a different response in the dorsal raphe as compared to ventral tegmental area and locus coeruleus: behavioral and concomitant neuronal recordings in adult rats

Methylphenidate (MPD) is a psychostimulant used to treat attention deficit hyperactivity disorder. MPD exerts its neurocognitive effects through increasing concentrations of dopamine (DA), norepinephrine (NE), and serotonin (5-HT) in the neuronal synapse. This study recorded from adult freely behaving rats a total of 1170 neurons, 403 from the ventral tegmental area (VTA), 409 from locus coeruleus (LC), and 356 from dorsal raphe (DR) nucleus, which are the main sources of DA, NE, and 5-HT to the mesocorticolimbic circuitry, respectively. Electrophysiological and behavioral activities were recorded simultaneously following acute and repetitive (chronic) saline or 0.6, 2.5, or 10.0 mg/kg MPD. The uniqueness of this study is the evaluation of neuronal activity based on the behavioral response to chronic MPD. Animals received daily saline or MPD administration on experimental days 1-6 (ED1-6), followed by a 3-day wash-out period, and then MPD rechallenge on ED10. Each chronic MPD dose elicits behavioral sensitization in some animals, while in others, behavioral tolerance. Neuronal excitation following chronic MPD was observed in brains areas of animals exhibiting behavioral sensitization, while neuronal attenuation following chronic MPD was observed in those animals expressing behavioral tolerance. DR neuronal activity was most affected in response to acute and chronic MPD administration and responded differently compared to the neurons recorded from VTA and LC neurons at all doses. This suggests that although not directly related, DR and 5-HT are involved in the acute and chronic effects of MPD in adult rats, but exhibit a different role in response to MPD.