The modulation of dopaminergic transmission in the striatum by MK-801 is independent of presynaptic mechanisms.

This paper reports biochemical and behavioural experiments, planned to obtain a deeper knowledge on the mechanisms of the facilitating action of dopaminergic transmission, induced by the NMDA-sensitive glutamate receptor antagonist, dizocilpine (MK-801). Single or repeated administrations of MK-801 (0.25 mg/kg, i.p., daily for 21 consecutive days) failed to change levels of either dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) in the striatum of the rat or the haloperidol-induced (0.125 mg/kg, i.p.) accumulation of DOPAC. Consistently, the NMDA antagonist, given at a dose which did not affect the spontaneous motility of the animal (0.125 mg/kg, i.p.), failed to potentiate the behavioural stimulatory effect, induced by the dopaminomimetic agents, methamphetamine or nomifensine. All these results, taken together, exclude a facilitating action of MK-801 on dopaminergic neurotransmission. The possibility that the stimulatory effect of MK-801 on dopaminergic neurones is indirect and independent of presynaptic mechanisms is discussed.