Behavioral and dorsal raphe neuronal activity following acute and chronic methylphenidate in freely behaving rats.

Concomitant behavioral and dorsal raphe (DR) neuronal activity were recorded following acute and chronic dose response of methylphenidate (MPD) in freely moving rats previously implanted with permanent semi-microelectrodes using telemetric (wireless) technology. On experimental day (ED) 1, the neuronal and locomotor activity were recorded after saline (baseline) and MPD (0.6, 2.5 or 10.0mg/kg) injection (i.p.). Animals were injected daily with a single dose of MPD for five consecutive days (ED 2-6) to elicit behavioral sensitization or tolerance. After three washout days, the neuronal and locomotor activity recording was resumed on ED 10 followed by saline and MPD rechallenge injection. The main findings were: (1) the same dose of chronic MPD administration elicited behavioral sensitization in some animals and behavioral tolerance in others. (2) 46%, 56% and 73% of DR units responded to acute 0.6, 2.5 and 10.0mg/kg MPD respectively. (3) 89%, 70% and 86% of DR units changed their baseline activity on ED 10 compared to that on ED 1 in the 0.6, 2.5 and 10.0mg/kg MPD groups respectively. (4) A significant difference in ED 10 baseline activity was observed in the DR neuronal population recording from animals expressing behavioral sensitization compared to that of animals expressing behavioral tolerance. (5) 89%, 78% and 88% of DR units responded to chronic 0.6, 2.5 and 10.0mg/kg MPD respectively. (6) The DR neuronal population recording following acute MPD on ED 1 and rechallenge MPD on ED 10 from animals expressing behavioral sensitization was significantly different from the neuronal population recorded from animals exhibited behavioral tolerance. The correlation between the DR neuronal activity and animal's behavior following chronic MPD exposure suggested that the DR neuronal activity may play an important role in the expression of behavioral sensitization and tolerance induced by chronic MPD administration.