THYROTROPIN-RELEASING-HORMONE (TRH) IS MARKEDLY INCREASED IN THE RAT-BRAIN FOLLOWING SOMAN-INDUCED CONVULSIONS

Soman is an organophosphorus (OP) compound which irreversibly inhibits acetylcholinesterase (AChE), the primary synaptic inactivator of acet ylcholine. Resultant excessive cholinergic activity elicits generalize d convulsions and brain lesions. Recent evidence suggests that other n eurotransmitter/neuromodulator systems may be affected by the OP compo unds as well. Since we have shown that both electrically and chemicall y induced seizures cause significant and prolonged increases in the ne uropeptide thyrotropin-releasing hormone (TRH) in epileptogenic sites, we examined soman-induced convulsion effects on CNS TRH. Rats were in jected with either soman (100 mu g/kg SC; equivalent to 0.9 LD(50)) or saline and observed for convulsive activity. Forty-eight hours post i njection, dramatic increases of TRH over control levels were seen in f rontal cortex (30-fold), pooled cortex (24-fold), hippocampus (16-fold ), piriform cortex (14-fold), entorhinal cortex (11-fold), and amygdal a (2-fold). No change was observed ip either hypothalamus or pituitary . Our results demonstrate, for the first time, a substantial effect of an OP on a specific neuropeptide system in vivo. The neurochemical an d behavioral consequences of the soman-induced increases in TRH, espec ially in the frontal cortex, are presently unknown. Clearly, much more work is required to discern the exact role TRH has following soman ex posure.