Subcortical deterioration after cortical damage: effects of diazepam and relation to recovery of function.
Agents which enhance the activity of gamma-aminobutyric acid (GABA) can severely disrupt behavioral recovery in rats following damage to the neocortex if delivered during a sensitive postoperative period. The mechanisms of this disruption have not been found. It has been suggested previously that the ipsilateral striatum and related structures may be transiently disabled after cortical lesions and that diazepam may interfere with restoration of function in these areas. In the present experiment, the subcortical anatomical effects of chronic (3 weeks) administration of diazepam, an indirect GABAergic agonist, were assessed following unilateral lesions of the anteromedial cortex (AMC) or the sensorimotor cortex (SMC) in rats. Atrophic and degenerative changes were examined in the striatum, substantia nigra and thalamus. Following either AMC or SMC lesions, there was a reduction in the size of the ipsilateral striatum and thalamus and a loss of neurons in the ipsilateral substantia nigra pars reticulata (SNr). After AMC lesions, striatal atrophy and neuron loss in the SNr were increased by the diazepam regimen relative to vehicle-treated controls. In addition, diazepam interfered with the behavioral recovery from somatic-sensorimotor asymmetries in AMC-lesioned rats. After SMC lesions, the sites of striatal and thalamic atrophy were different from that observed after AMC lesions, and the extent of atrophy and neuron loss was not exaggerated by diazepam treatment. Consistent with these data, diazepam did not significantly affect recovery from SMC lesions. These findings suggest that the long-term disruptive effects of diazepam on recovery of function after AMC lesions may be related to an augmentation of lesion-induced degeneration.
Jones
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TA
Department of Psychology, University of Texas, Austin 78712.
Schallert
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D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology; D003975:Diazepam / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013003:Somatosensory Cortex / Q000187:drug effects / Q000503:physiopathology; D013378:Substantia Nigra / Q000187:drug effects / Q000503:physiopathology; D013788:Thalamus / Q000187:drug effects / Q000503:physiopathology
D003975:Diazepam