Effects of HI-6 and pralidoxime on neuronal RNA in thalamic cholinergic sites

Quantitative azure B-RNA cytophotometry was employed to compare effects of the oximes HI-6 and pralidoxime (2-PAM) to those of atropine sulfate (AS) on neuronal RNA metabolism in the thalamic ventrobasal nuclear complex (VBC) and nucleus reticularis (NR). The ability of these compounds to mitigate soman (pinacolyl methylphosphonofluoridate)-induced neuronal RNA alterations (i.e., VBC-RNA depletion/NR-RNA elevation) in these muscarinic cholinergic sites was also determined. Generally, HI-6 (125 mg/kg, i.p.) and 2-PAM (43.2 mg/kg, i.m.) elicited similar patterns of neuronal RNA changes, i.e., diminution of VBC-RNA and NR-RNA with oximes alone; partial amelioration of soman (1.5 LD50, s.c.)-induced VBC-RNA loss; and slight or no effect on soman induced NR-RNA accumulation. HI-6 produced more severe RNA reduction than 2-PAM in both brain regions of non-poisoned rats, whereas 2-PAM was more effective in reversing the effects of soman in these two regions. The muscarinic antagonist, AS, also produced VBC-RNA depletion and partially counteracted the VBC-RNA loss in soman intoxicated rats. Unlike the oximes, however, AS resulted in NR-RNA accumulation and it also antagonized soman induced NR-RNA elevation. Neither oxime reactivated soman inhibited brain acetylcholinesterase but HI-6 did reactivate appreciable plasma cholinesterase. The overall data suggest that HI-6 and 2-PAM do exert pharmacologic actions on cholinergic neurons in the rat CNS. However, the greater effectiveness of HI-6 over 2-PAM in countering lethal actions of soman does not appear to be correlated with oxime mediated restoration of neuronal RNA levels in these two cholinergic regions.(ABSTRACT TRUNCATED AT 250 WORDS)