4 WEEKS INHALATION EXPOSURE OF RATS TO P-CYMENE AFFECTS REGIONAL AND SYNAPTOSOMAL NEUROCHEMISTRY

Long-lasting effects of inhalation exposure to p-cymene (p-isopropyl-t oluene; CAS No. 99-87-6) on regional and subcellular brain neurochemis try 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 exp osure-free period of 8 weeks. Synaptosomes were isolated from whole br ain minus cerebellum and used as an ex situ model for in situ conditio ns at the level of the presynaptic nerve terminal. There was no persis tent effect on wet weight (regional) or regional noradrenaline (NA), d opamine (DA), or 5-hydroxytryptamine (5-HT) concentrations owing to ex posure. 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, m ean+/-1 S.D.). Synaptosomal NA and DA concentrations and acethycholine sterase, butyrylcholinesterase, and lactate dehydrogenase activities w ere statistically significantly increased when expressed relative to s ynaptosomal protein. It is hypothesized that a reduced density and num ber of synapses in situ are functionally compensated for by increased NA and DA release from noradrenergic and dopaminergic presynaptic nerv e terminals. The applicability of the synaptosome as an ex situ neuroc hemical research model for the presynaptic CNS nerve terminal in situ for the study of solvent neurotoxicity in rats was further supported.