Dystonic posturing and circling behaviors induced by dopaminergic agents in rats with unilateral globus pallidus lesions.
The present study examined the behavioral effects of dopamine receptor agonists, antagonists, or N-methyl-D-aspartate (NMDA) glutamate receptor antagonist in rats with a unilateral excitotoxic lesion of the globus pallidus (GP). After the unilateral GP lesions were made by injections of the ibotenic acid, drugs were systemically given and the elicited behaviors were quantitatively assessed. Systemic administration of haloperidol, but not SCH23390, dose-dependently induced contraversive dystonic posturing in unilateral GP-lesioned rats. On the other hand, systemic administration of quinpirole, but not SKF38393, induced ipsiversive circling. MK-801, only when given at a high dose, unilateral GP-lesioned rat, the D2 receptor agonist and antagonist caused ipsiversive and contraversive posturing or circling, respectively. Since the rotational behavior is induced on the basis of asymmetry of the basal ganglia output activity, there must be a marked difference between the GP ablation and the administration of D2 receptor blockade on the basal ganglia output activity, supporting a speculation that overactivity of the basal ganglia under dopamine depletion is not solely a result of the disinhibition from the inhibitory GP efferents. The present unilateral GP-lesion model appears to be a useful one for the pharmacobehavioral investigation of D2-mediated mechanisms.
Miwa
H
H
Department of Neurology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu-city, Tokyo 183, Japan. h_miwa@med.juntendo.ac.jp
Nishi
K
K
Fuwa
T
T
Mizuno
Y
Y
D000704:Analysis of Variance; D000818:Animals; D015259:Dopamine Agents / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004421:Dystonia / Q000139:chemically induced*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007839:Functional Laterality / Q000502:physiology*; D005917:Globus Pallidus / Q000187:drug effects*; D008297:Male; D011187:Posture / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012399:Rotation; D009435:Synaptic Transmission / Q000187:drug effects*
D015259:Dopamine Agents; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate