Intra-nigra infusion of AMPA attenuates dopamine-dependent rotation in the rat.
It has previously been shown that glutamatergic overactivity of the subthalamic nucleus (STN) is involved in hypokinetic movement disorders such as Parkinson's disease. Conversely, it has been hypothesized that hyperkinetic behavioral syndromes may be associated with reduced glutamatergic transmission of the STN to its target areas, the substantial nigra pars reticulata (SNR) and the globus pallidus pars interna (GPI). In the present experiment, apomorphine injected systemically into unilaterally dopamine-denervated rats induced the hyperkinetic syndrome of contralateral rotation. The involvement of glutamatergic input to the SNR in this hyperkinesia was investigated by pharmacological manipulation with an agonist or an antagonist at the AMPA subtype of glutamate receptors. Either the agonist AMPA or the antagonist CNQX was infused directly into the SNR at a dose of 1.0 nmol. Intra-SNR AMPA attenuated the contralateral rotation induced by apomorphine without eliciting any effects on rotation by itself. Infusions of the antagonist CNQX did not affect either apomorphine-induced or spontaneous rotation. These results support the notion that underactivity of the SNR and its glutamatergic afferent projection from the STN may underlie hyperkinetic movement disorders and that local stimulation of the AMPA subtype of glutamate receptors can ameliorate such syndromes.
Burns
L H
LH
Neuroregeneration Laboratory, McLean Hospital, Belmont.
Sato
K
K
Wüllner
U
U
Isacson
O
O
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists; D007267:Injections; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D012399:Rotation; D013239:Stereotyped Behavior / Q000502:physiology*; D013378:Substantia Nigra; D013787:Thalamic Nuclei / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000276:immunology / Q000378:metabolism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000008:administration & dosage / Q000494:pharmacology*
D015259:Dopamine Agents; D018492:Dopamine Antagonists; D011810:Quinoxalines; D018091:Receptors, AMPA; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine; D004298:Dopamine