Article date: 1985/11/18
PubMed ID: 2998553
Journal name: Brain research (ISSN: 0006-8993)
A mutant strain of Wistar rats which carries an autosomal gene defect is characterized by a progressively developing hyperexcitability, tremor, olfactory and gustatory movements, bradykinesia, ataxia and a pathologically increased muscle tone of hindlimbs which can be measured by recording tonic activity in the electromyogram (EMG) of the gastrocnemius-soleus muscle. The activity of the GABA synthesizing enzyme glutamic acid decarboxylase (GAD) and the receptor binding of GABA as estimated by [3H]GABA binding to synaptic membranes were examined in olfactory bulbs, frontal cerebral cortex, corpus striatum, hippocampus, thalamus, hypothalamus, tectum, substantia nigra, medulla oblongata, cerebellum, and pons of mutant rats. Mutant rats exhibit a lower activity of GAD in synaptosomal fractions of olfactory bulbs and substantia nigra whereas GAD activity within the pons was increased. The changes in the activity of GAD were accompanied by alterations in [3H]GABA binding to synaptic membranes: GABA binding was significantly elevated in the olfactory bulbs and the substantia nigra, but it was markedly reduced in the pons. The functional importance of impaired nigral GABAergic transmission in mutant rats was demonstrated by the fact that intranigral injection of the GABA agonist muscimol reduced the tonic extension of the hindlimbs as indicated by reduced tonic EMG activity of the gastrocnemius-soleus muscle, while intranigral injection of the GABA antagonist bicuculline increased the disturbance.
Author List: Schwarz M, Löscher W, Turski L, Sontag K H
Publication Types: Journal Article; Research Support, Non-U.S. Gov't
Substances mentioned in the article: Receptors, GABA-A; Muscimol; gamma-Aminobutyric Acid; Glutamate Decarboxylase; Bicuculline;
Mesh terms: Animals; Basal Ganglia Diseases/physiopathology; Bicuculline/pharmacology; Brain Chemistry; Electromyography; Female; Glutamate Decarboxylase/metabolism; Male; Muscimol/pharmacology; Muscles/physiopathology; Rats; Rats, Inbred Strains/genetics; Rats, Mutant Strains; Receptors, GABA-A/drug effects; Substantia Nigra/physiopathology; Synaptic Transmission/drug effects; Synaptosomes/enzymology; Time Factors; gamma-Aminobutyric Acid/metabolism;