Segmental synaptic depression caused by diisopropylphosphorofluoridate and sarin is reversed by thyrotropin-releasing hormone in the neonatal rat spinal cord

The organophosphorus compounds diisopropylphosphorofluoridate (DFP) and isopropylmethylphosphonofluoridate (sarin) depressed the monosynaptic reflex (MSR) in spinal cords from 7- to 9-day-old male rats. The concentrations of DFP and sarin which depressed the MSR by nearly 50% were 100 microM and 100 nM, respectively. Simultaneous superfusion of the cords with thyrotropin-releasing hormone (TRH) with either DFP or sarin resulted in a reversal of the depression. The depression caused by DFP was reversed to 95% of control by 100 nM TRH whereas similar reversal of sarin-induced depression required a 10-fold greater concentration of TRH. The potentiating effect of TRH was not affected by atropine even at a high concentration (1 microM) although atropine easily reversed organophosphorus-induced depression of the MSR. It appears that reversal of organophosphorus-induced depression by TRH might occur through a noncholinergic, TRH-sensitive receptor mechanism and may be unrelated to acetylcholinesterase activity. This action represents a possible utility of TRH as an adjunct in organophosphorus toxicity.