Electrophysiological effects of MK-801 on rat nigrostriatal and mesoaccumbal dopaminergic neurons.
The electrophysiological effects of the non-competitive N-methyl-D-aspartate (NMDA) antagonist (+)-MK-801 (MK-801) on nigrostriatal and mesoaccumbal dopaminergic (DA) neurons were evaluated in chloral hydrate-anesthetized rats. MK-801 (0.05-3.2 mg/kg, i.v.) stimulated the firing rates of 14 (74%) of 19 nigrostriatal DA (NSDA) neurons and all 16 mesoaccumbal DA (MADA) neurons tested. Stimulatory effects of the drug were more prominent on MADA neurons. Interspike interval analysis revealed that MK-801 also regularized DA neuronal firing pattern. Acute brain hemitransection between the midbrain and forebrain attenuated the stimulatory effects of MK-801 on firing rate and blocked the effects on firing pattern. Similar to MK-801, hemitransection itself increased NSDA and MADA cell firing rates and regularized firing pattern. Both i.v. and iontophoretic MK-801 blocked the excitatory effects of iontophoretic NMDA but did not affect excitations caused by the non-NMDA glutamatergic receptor agonists quisqualate and kainate. Iontophoretic MK-801 had no effect alone. These results suggest that the excitatory effects of i.v. MK-801 on DA neuronal activity are not due to direct actions on DA neurons. Glutamatergic projections originating anterior to the hemitransection appear to play a role in the effects of MK-801 on DA neuronal activity.
Zhang
J
J
Department of Psychiatry, Wayne State University School of Medicine, Detroit, MI 48201.
Chiodo
L A
LA
Freeman
A S
AS
D000818:Animals; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D005071:Evoked Potentials / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D009474:Neurons / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects*
D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D004298:Dopamine