Postural effects of unilateral blockade of glutamatergic neurotransmission in the subthalamic nucleus on haloperidol-induced akinesia in rats.
The present study examined the postural effects of the local application of glutamatergic antagonists unilaterally into the subthalamic nucleus (STN), on haloperidol-induced akinesia in rats. After intracerebral injections of MK-801, a selective antagonist of N-methyl-D-aspartate (NMDA) receptor, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) disodium, a selective alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor antagonist, or vehicle, unilaterally into the STN, haloperidol was administered systemically and the elicited behaviors were assessed quantitatively. In rats which received injections of MK-801 or CNQX, but not vehicle, unilaterally into the STN, the administration of haloperidol induced contraversive dystonic posturing. The severity of the deviated posturing was dose-dependent. The present findings revealed that the overactivity of the STN under conditions of dopamine blockade is suppressed by interruptions of glutamatergic inputs, mediated via both NMDA or AMPA receptors, to the STN. Therefore, the present study may provide functional evidence in support of a recently proposed hypothesis, that not only disinhibition from the inhibitory globus pallidus efferents but also excitatory glutamatergic inputs to the STN actually contribute to the overactivity of the STN under dopamine-depleted conditions.
Miwa
H
H
Department of Neurology, Tokyo Metropolitan Institute for Neuroscience, Fuchu-city, Japan. h_miwa@med.juntendo.ac.jp
Nishi
K
K
Fuwa
T
T
Mizuno
Y
Y
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D018726:Anti-Dyskinesia Agents / Q000633:toxicity*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007839:Functional Laterality / Q000502:physiology; D006220:Haloperidol / Q000633:toxicity*; D008297:Male; D009069:Movement Disorders / Q000209:etiology*; D011187:Posture / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D009435:Synaptic Transmission / Q000187:drug effects*; D013787:Thalamic Nuclei / Q000187:drug effects*
D018726:Anti-Dyskinesia Agents; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D006220:Haloperidol