Trimethylolpropane phosphate induces epileptiform discharges in the CA1 region of the rat hippocampus

The actions of trimethylolpropane phosphate (TMPP), an ethyl bicyclophospha te convulsant produced during the partial pyrolysis of some phosphate ester -based lubricants, were tested on CA1 neurons of rat hippocampal slices usi ng intracellular recording techniques. Bath application of TMPP (0.1-100 mu M) induced spontaneous paroxysmal depolarizing shifts and the associated sp ontaneous epileptiform bursts followed by after-hyperpolarizations in 63% o f neurons tested. The TMPP-induced epileptiform bursts were blocked by musc imol, a gamma -aminobutyric acid A (GABA(A)) receptor agonist, diazepam (DZ P), a GABA(A)-benzodiazepine ionophore complex agonist, or baclofen, a GABA (B) receptor agonist. While bath application of muscimol, DZP, or baclofen suppressed spontaneous activity in CA1 neurons not previously exposed to TM PP, subsequent application of TMPP (10 muM) reversed the actions of muscimo l and diazepam, but not baclofen. TMPP (0.1-100 muM) also induced membrane hyperpolarization associated with an increase in peak input resistance and inward rectification in 33% of neurons tested or membrane depolarization as sociated with an increase in input resistance in 17% of neurons tested. In summary, TMPP induced epileptiform activities in hippocampal CA1 neurons. T he epileptogenic effects of TMPP are consistent with its interaction with G ABA(A)-benzodiazepine receptors. (C) 2001 Academic Press.