GABAergic and cholinergic indices in various regions of rat brain after intracerebral injections of folic acid

Abstract

Unilateral lesions were induced in the substantia innominata (SI) of rats by 3 methods: electrocoagulation, 2 nmol kainic acid (KA) injection or 50–200 nmol folic acid (FA) injection. Histological examination by cresyl violet and GABA-transaminase staining and biochemical evaluation by glutamic acid decarboxylase (GAD) and choline acetyltransferase (ChAT) measurement were undertaken of the SI and several remote areas. Injections of FA into the SI produced much less local but more severe distant neuronal damage than did injections of KA. Both produced sustained epileptiform activity. Electrolytic lesions, on the other hand, produced only local neuronal damage and no epileptiform activity. Biochemical measurements of GAD and histochemical staining for GABA transaminase indicated many of the neurons in the distant areas affected following FA injections were GABAergic, but cholinergic neurons were relatively spared. Damage to the cortical areas was heaviest in the superficial layers. Dose-related losses were seen in GAD in a number of regions, with the most severe distant damage being in the amygdala and pyriform cortex and significant but lesser extent in the frontal, entorhinal and temporal cortices, and in the thalamus. The striatum and hippocampus were spared. The distant damage, except in the thalamus, seemed to parallel the density of cholinergic innervation from the SI as revealed by relative drops in ChAT following KA injections into the SI. Reduction in both seizure-like activity and remote damage was brought about by pretreatment of the animals with valium (20 mg/kg) or scopolamine (50 mg/kg). The protective action of scopolamine is consistent with the possibility that cholinergic neurons may mediate much of the remote damage to GABA neurons, although they themselves are little affected. Distant effects of injections of FA into the striatum were comparable in kind but much less in magnitude to those after SI injection while amygdala injections of FA did not produce significant losses in GAD in any of the regions examined.