MAPPING OF CEREBRAL METABOLIC-ACTIVATION IN 3 MODELS OF CHOLINERGIC CONVULSIONS

Glucose utilization of four cerebral cortex and 35 subcortical regions (CGU) was analyzed in three models of cholinergic seizures induced by the following compounds: 1) soman (pinacolylmethylphosphonofluoridate ) an organophosphorus cholinesterase inhibitor, 100 mu g/kg SC after p retreatment with pyridostigmine 26 mu g/kg IM (n = 6); 2) physostigmin e, a carbamate cholinesterase inhibitor, 1.31 mg/kg infused IV over 75 min (n = 6); and 3) pilocarpine, a direct cholinergic agonist, 30 mg/ kg SC (n = 6), Physostigmine and pilocarpine were preceded by 3 mmol/k g LiCl IP 20 hrs earlier, Animals injected with saline SC (n = 6) were used as controls, Step-wise discriminant analysis successfully classi fied 100% of the cases into the four experimental groups with data fro m only six regions, Pyridostigmine-soman induced the most widespread a nd greatest increases in CGU. More restricted and lower levels of acti vation were observed with Li-pilocarpine while Li-physostigmine induce d significant increases in CGU only in globus pallidus, entopeduncular nucleus, and substantia nigra, These three regions, which are functio nally related, were also activated in the other two models of choliner gic convulsions and may represent the initial step in cholinergic acti vation of the CNS, Li-pilocarpine failed to activate most of the brain stem and the superior colliculus. All cortical regions were activated by Li-pilocarpine and pyridostigmine-soman, while they were inhibited by Li-physostigmine. This phenomenon may be due in part to the lack of activation with physostigmine of the basal forebrain nuclei (lateral septum, medial septum, vertical and horizontal limbs of the diagonal b and, and substantia innominata) resulting in a decreased drive of cort ical metabolism. (C) 1998 Elsevier Science Inc.