Increased responsivity of glutamate release from the substantia nigra pars reticulata to striatal NMDA receptor blockade in a model of Parkinson's disease. A dual probe microdialysis study in hemiparkinsonian rats.
Dual probe microdialysis was employed in freely moving 6-hydroxydopamine (6-OHDA) hemilesioned rats to investigate the effects of blockade of N-methyl-D-aspartate (NMDA) receptors in the dorsolateral striatum on glutamate (Glu) release from the ipsilateral substantia nigra pars reticulata (SNr). Perfusion for 60 min with the NMDA antagonist dizocilpine (0.1 and 1 microM) in the dopamine (DA)-denervated striatum stimulated nigral Glu release (peak effect of 139 +/- 7% and 138 +/- 9%, respectively). The lower (0.01 microM) and higher (10 microM) concentrations were ineffective. In sham-operated rats, dizocilpine failed to affect nigral Glu release up to 1 microM but induced a prolonged stimulation at 10 microM (153 +/- 9% at the end of perfusion). The present results show that DA-deficiency in the striatum of hemiparkinsonian rats is associated with increased responsivity of nigral Glu release to striatal NMDA receptor blockade. This suggests that changes of NMDA receptor mediated control of the striatofugal pathways occur during Parkinson's disease (PD).
Marti
M
M
Section of Pharmacology, Department of Experimental and Clinical Medicine, University of Ferrara, Ferrara, Italy.
Sbrenna
S
S
Fuxe
K
K
Bianchi
C
C
Beani
L
L
Morari
M
M
D000818:Animals; D003342:Corpus Striatum / Q000502:physiology* / Q000503:physiopathology; D003714:Denervation; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology*; D007839:Functional Laterality; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000502:physiology*; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000503:physiopathology*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*
D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D016627:Oxidopamine