Dorsal raphe neuronal activities are modulated by methylphenidate

This study investigated the electrophysiological properties of the dorsal raphe nucleus (DR) neurons in response to the acute and repetitive administration of methylphenidate (MPH). Activities of DR neurons were recorded from non-anesthetized, freely behaving rats previously implanted bilaterally with permanent semi microelectrodes. The main findings were: (1) after initial (acute) administration of MPH (2.5 mg/kg i.p.) on experimental day one (ED1), 56 % of DR units significantly changed their firing rates. The majority of the responsive units (88 %) exhibited increased firing rate; (2) daily MPH injections were given on ED2 through ED6 followed by 3 washout days. On ED10, 83 % of the DR units significantly changed their baseline activity compared to the baseline activity on ED1; (3) after rechallenge MPH administration on ED10, 63 % of DR units exhibited significant change in their firing rate; the majority of the responsive units (76 %) exhibited a significant increase in their firing rate; (4) The effect of rechallenge MPH administration on ED10 was compared to the effect of initial MPH on ED1, 47 % DR units exhibited a further significant increase in their firing rate while 53 % DR units exhibited decrease or non-change in their firing rate which can be interpreted as electrophysiological sensitization or tolerance. In conclusion, this study demonstrated that acute MPH administration modulated the DR neuronal activities. Repetitive MPH administration modulated the baseline activities of DR units and elicited neurophysiological sensitization or tolerance. The results indicated that MPH affects DR neuronal activity.