Multilevel transneuronal degeneration after brain damage. Behavioral events and effects of anticonvulsant gamma-aminobutyric acid-related drugs.
Recent morphologic and behavioral studies of the effects of gamma-aminobutyric acid agents on transsynaptic degeneration after cortical and striatal damage are reviewed and discussed. Following unilateral lesions of the anteromedial cortex, mild atrophy appears in the ipsilateral striatum and substantia nigra pars reticulata. Long-term diazepam administration greatly enhances this degeneration, extends the degeneration into the thalamus, and severely disrupts recovery from somatosensory asymmetries. Following unilateral excitotoxic lesions of the striatum, progressive degeneration of neurons occurs in the substantia nigra pars reticulata and efferent targets in the thalamus. This degeneration can be prevented by chronic infusion of muscimol, a gamma-aminobutyric acid agonist. Unexpectedly, this treatment did not facilitate recovery from somatosensory asymmetries. Recovery in muscimol-treated animals was impaired relative to saline-treated controls. Thus, gamma-aminobutyric acid agonists either may enhance or prevent neural atrophy secondary to brain damage, but the behavioral outcome appears to depend importantly on the excitatory and inhibitory characteristics of the affected networks.
Schallert
T
T
Department of Psychology, University of Texas, Austin 78712.
Jones
T A
TA
Lindner
M D
MD
D000818:Animals; D001284:Atrophy; D001522:Behavior, Animal / Q000187:drug effects; D002561:Cerebrovascular Disorders / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D003342:Corpus Striatum / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology; D009118:Muscimol / Q000494:pharmacology; D009434:Neural Pathways; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D051381:Rats; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013788:Thalamus / Q000187:drug effects / Q000473:pathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D003975:Diazepam