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.
Gandolfi
O
O
Department of Pharmacology, University of Bologna, Italy.
Rimondini
R
R
Dall'Olio
R
R
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009627:Nomifensine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
D015102:3,4-Dihydroxyphenylacetic Acid; D009627:Nomifensine; D008694:Methamphetamine; D016291:Dizocilpine Maleate; D006220:Haloperidol; D004298:Dopamine