ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract: Previous pharmacological studies have indicated that impairment of GABAergic transmission may be involved in the pathophysiology of dystonia in the mutant dtsz hamster, i.e., a genetic animal model for idiopathic dystonia. In the present experiments, the kinetic constants of [3H]flumazenil binding to the benzodiazepine site of the GABAA receptor were calculated from equilibrium binding measurements in various brain regions of genetically dystonic hamsters and age-matched controls. Because dystonia in mutant dtsz hamsters is transient and disappears after ∼60–70 days of age, [3H]flumazenil binding was studied at the age of maximum severity of dystonia (30–40 days) and after disappearance of the disease, to examine which neurochemical changes were related to dystonia. In mutant hamsters with the maximum severity of dystonia, receptor affinity of [3H]flumazenil was increased in olfactory bulb,striatum, tectum, and cerebellum, as exemplified by significantly decreased dissociation constants (KD) in these regions. An increased number of binding sites (Bmax) were seen in striatum and frontal cortex but not in the other eight regions studied in this regard. All these changes in [3H]flumazenil binding disappeared in parallel with dystonia, implicating a causal relationship between altered benzodiazepine receptor binding and dystonia in mutant dtsz hamsters. In view of the antidystonic effect of benzodiazepines, such as diazepam, and recent neurochemical findings indicating impaired function of the GABA-gated Cl− channel in dystonic hamsters, the present data might be interpreted as up-regulation of benzodiazepine receptors in response to impaired GABAergic function. Furthermore, the present data represent the first evidence that GABAA receptors are altered in the basal ganglia in idiopathic (primary)dystonia.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.1995.64052153.x
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