NMDA receptor antagonist disrupts acute and chronic effects of methylphenidate

Methylphenidate (MPD) is a drug widely used for treating attention-deficit/hyperactivity disorder in children. Because of its extensive consumption and because it has pharmacological stimulant properties similar to amphetamine and cocaine, MPD has the potential of abuse. N-methyl-D-aspartate (NMDA) receptors are suggested to be involved in CNS effects of stimulants, and antagonists of the NMDA receptor can potentially alter the stimulants' effects. Dizocilpine (MK-801), a non-competitive antagonist of the NMDA receptor, has been reported to prevent sensitization elicited by repeated administration of amphetamine and cocaine. The objective of the present study was to use the tail-flick latency assay, rectal temperature, and body weight gain to assess effects of repetitive treatment of MPD and whether MK-801 treatment would alter these effects in Sprague-Dawley rats. It was found that: (Ia) Acute administration of MPD or MK-801 did not alter the tail-flick latency, (Ib) Repeated administration of MPD decreased tail-flick latency, while repeated administration of MK-801 had no significant effect on tail-flick latency, (Ic) MK-801 given prior to or with MPD reversed the chronic effect on tail-flick latency produced by MPD; (IIa) When both drugs were independently given, MPD elicited a decrease in rectal temperature, while MK-801 alone produced an increase in temperature, (IIb) When given together, MK-801 had a transient effect in blocking the sensitization to MPD but failed to reverse the sensitization of MPD once it had developed; and (III) Both MK-801 and MPD caused an unstable pattern of body weight gain. Hence, the results of this study in rats suggest that MK-801 can modulate non-motor effects of MPD.