Methylphenidate enhances noradrenergic transmission and suppresses mid- and long-latency sensory responses in the primary somatosensory cortex of awake rats.

Noradrenergic neurons send widespread projections to sensory networks throughout the brain and regulate sensory processing via norepinephrine (NE) release. As a catecholamine reuptake blocker, methylphenidate (MPH) is likely to interact with noradrenergic transmission and NE modulatory action on sensory systems. To characterize the neurochemical actions of MPH in the primary sensory cortex of freely behaving rats and their consequences on sensory processing, we measured extracellular NE levels in the primary somatosensory (SI) cortex by microdialysis and recorded basal and sensory-evoked discharge of infragranular SI cortical neurons, before and after intraperitoneal administrations of saline or MPH (1 and 5 mg/kg). Both doses of MPH significantly increased NE levels in the SI cortex (+64 and +101%, respectively). In most neurons, stimulation of the whisker-pad induced a triphasic response, consisting of a short-latency excitation [4.7 +/- 0.2 (SE) ms] followed by a postexcitatory inhibition (36 +/- 1.5 ms) and a long-latency excitation (105 +/- 2.6 ms). Under control conditions, the behavioral state of the animal was correlated with the magnitude of the short-latency excitation but not with other aspects of the basal and sensory-evoked discharge of SI cortical neurons. At 5 mg/kg, MPH significantly increased locomotor activity and induced a significant suppression of the short-latency excitation, which probably resulted from the MPH-induced change in behavior. In addition, both doses of MPH suppressed the postexcitatory inhibition and the long-latency excitation evoked by the stimulation of the whisker pad. These effects did not seem to result from the locomotor effect of MPH and probably involved MPH-induced enhancement of noradrenergic transmission.