Neurochemical profile of effects of 28 neurotoxic chemicals on the central nervous system in rats (1). Effects of oral administration on brain contents of biogenic amines and metabolites.

We investigated the effects of oral administration of 28 organic chemical agents, all of which possess neurotoxicity and most of which are used as industrial solvents, on monoamine neurotransmitters and metabolites in the rat brain. Each chemical was administered to rats singly at a dose of one-quarter the LD50 value. Two hours after administration, acetylcholine, 3,4-dihydroxyphenylalanine (DOPA), dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), norepinephrine, 3-methoxy-4-hydroxyphenylglycol (MHPG), serotonin, and 5-hydroxyindoleacetic acid (5HIAA) contents in the small-brain regions were measured. Twenty-one of the 28 chemicals increased acetylcholine in the hippocampus, a ratio (21/28) far higher than the 0.5 expected were these chemicals to have no tendency to increase or decrease acetylcholine. This ratio was calculated for each brain substance. Large differences from 0.5 were also obtained for DOPAC (higher), and for 5HIAA and three neurotransmitters (dopamine, norepinephrine, and serotonin) in the hypothalamus (all lower). The ratios for MHPG and 5HIAA in the medulla oblongata were very high. In the hypothalamus, the concentrations of brain substances were easily altered by the test chemicals, and the turnover rates of hypothalamic norepinephrine and serotonin in the medulla oblongata seemed to be accelerated. Several lines of evidence obtained in previous studies suggest that the increased acetylcholine content in the brain homogenate induced by organic solvents such as toluene may be due to a decrease in acetylcholine release from nerve terminals. Based on the results of the present experiment and previous studies, this acetylcholine suppressing property appears to be common to solvents which possess anesthetic properties.