title: Thyrotropin-releasing hormone (TRH) is markedly increased in the rat brain following soman-induced convulsions.
abstract: Soman is an organophosphorus (OP) compound which irreversibly inhibits acetylcholinesterase (AChE), the primary synaptic inactivator of acetylcholine. Resultant excessive cholinergic activity elicits generalized convulsions and brain lesions. Recent evidence suggests that other neurotransmitter/neuromodulator systems may be affected by the OP compounds as well. Since we have shown that both electrically and chemically induced seizures cause significant and prolonged increases in the neuropeptide thyrotropin-releasing hormone (TRH) in epileptogenic sites, we examined soman-induced convulsion effects on CNS TRH. Rats were injected with either soman (100 microg/kg SC; equivalent to 0.9 LD50) or saline and observed for convulsive activity. Forty-eight hours post injection, dramatic increases of TRH over control levels were seen in frontal cortex (30-fold), pooled cortex (24-fold), hippocampus (16-fold), piriform cortex (14-fold), entorhinal cortex (11-fold), and amygdala (2-fold). No change was observed in 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 and behavioral consequences of the soman-induced increases in TRH, especially in the frontal cortex, are presently unknown. Clearly, much more work is required to discern the exact role TRH has following soman exposure.
authors.affiliation: Department of Anatomy, Indiana University School of Medicine, Indianapolis 46202-5120, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Kubek
authors.forename: T M
authors.initials: TM
authors.lastname: Shih
authors.forename: J L
authors.initials: JL
authors.lastname: Meyerhoff
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002800:Cholinesterase Inhibitors; D004353:Drug Evaluation, Preclinical; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D012999:Soman; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism*
chemical_list: D002800:Cholinesterase Inhibitors; D013973:Thyrotropin-Releasing Hormone; D012999:Soman