Long-term impairment of behavioral recovery from cortical damage can be produced by short-term GABA-agonist infusion into adjacent cortex.

Diazepam and other GABA-related agents can prevent or delay recovery from an otherwise short-term somatosensory asymmetry caused by unilateral cortical lesions. Postrecovery treatment does not affect behavior. One possible contributive site of action for these agents is remaining cortical tissue. In the present study, following unilateral anteromedial cortex (AMC) lesions or sham operations, the GABA agonist muscimol or saline was infused once a day for 7 days into the adjacent sensorimotor cortex (SMC) or, as a control, into the more remote occipital cortex (OC) of the ipsilateral hemisphere. Each day the animals were given somatosensory and motor coordination tests at 21 h postinfusion. The SMC-muscimol regimen, but not the SMC-saline or OC-muscimol, retarded recovery from somatosensory asymmetry. The disruptive effect on recovery was enduring, greatly outlasting the week of exposure to muscimol. In sham-operated animals, SMC-muscimoI did not yield a chronic effect on behavior, although during the first hour after each infusion, in which the muscimol presumably was still present in the SMC, somatosensory asymmetry could be observed. Although the AMC lesion created a vulnerability to muscimol in the SMC, no detectable difference in the extent of cortical damage in this group could account for the prolongation of behavioral asymmetry. SMC-muscimol (but not SMC-saline) led to atrophy of SMC projection areas in the ipsilateral thalamus. However, in sham-operated animals, SMC-muscimol did not affect thalamic size. These behavioral and anatomical data suggest that systemically delivered GABAergic drugs might interfere with restoration of function after AMC lesions in part by adversely influencing events in the SMC.