Lam_1996_Pharmacol.Toxicol_79_225

Long-lasting effects of inhalation exposure to p-cymene (p-isopropyl-toluene; CAS No. 99-87-6) on regional and subcellular brain neurochemistry were studied. Male Long-Evans rats were exposed to 0, 50, or 250 p.p.m. p-cymene 6 hr/day, 5 days/week for four weeks followed by an exposure-free period of 8 weeks. Synaptosomes were isolated from whole brain minus cerebellum and used as an ex situ model for in situ conditions at the level of the presynaptic nerve terminal. There was no persistent effect on wet weight (regional) or regional noradrenaline (NA), dopamine (DA), or 5-hydroxytryptamine (5-HT) concentrations owing to exposure. Yield of synaptosomal protein was statistically significantly reduced in an exposure concentration-related manner (Control: 16.6 +/- 3.1; 50 p.p.m.: 9.2 +/- 2.1; 250 p.p.m.: 8.6 +/- 1.7 mg protein/g tissue, mean +/- I.S.D.). Synaptosomal NA and DA concentrations and acethycholinesterase, butyrylcholinesterase, and lactate dehydrogenase activities were statistically significantly increased when expressed relative to synaptosomal protein. It is hypothesized that a reduced density and number of synapses in situ are functionally compensated for by increased NA and DA release from noradrenergic and dopaminergic presynaptic nerve terminals. The applicability of the synaptosome as an ex situ neurochemical research model for the presynaptic CNS nerve terminal in situ for the study of solvent neurotoxicity in rats was further supported.