ACUTE EFFECTS OF A BICYCLOPHOSPHATE NEUROCONVULSANT ON MONOAMINE NEUROTRANSMITTER AND METABOLITE LEVELS IN THE RAT BRAIN

Naive male Sprague-Dawley rats were injected intraperitoneally (ip) with the bicyclophosphate convulsant trimethylolpropane phosphate (TMPP) at dose levels from 0.2 to 0.6 mg/kg. Rats were observed for convulsive activity, and were sacrificed 15 min posttreatment. Levels of the monoamine neurotransmitters norepinephrine (NE), epinephrine (EPI), dopamine (DA) , and serotonin (5-HT) and the major metabolites 3,4- dihydroxyphenylacetic acid ( DOPAC) , homovanillic acid ( HVA) , and 5-hydroxyindoleacetic acid ( 5-HIAA) were assayed in forebrain, midbrain, hindbrain, cerebellum and brainstem regions. Neurotransmitter and metabolite levels were compared between control rats and rats that did and did not experience seizures. TMPP administration induced significant decreases in levels of measured neurotransmitters that varied as a function of brain region, dose, and expression of the seizure activity. These results show that tonic or tonic-clonic seizures induced by TMPP administration (0.6 mg/ kg) are reliably associated with regional decreases in serotonin, dopamine, and norepinephrine. Convulsive activity resulting from lower dose administrations (0.2-0.4 mg/kg) of TMPP result only in decreased regional levels of serotonin.