Effects of white spirits on rat brain 5-HT receptor functions and synaptic remodeling.
Previously, inhalation exposure to different types of white spirit (i.e. complex mixtures of aliphatic, aromatic, alkyl aromatic, and naphthenic hydrocarbons) has been shown to induce neurochemical effects in rat brains. Especially, the serotonergic system was involved at the global, regional, and subcellular levels. This study investigates the effects of two types of white spirit on 5-hydroxytryptamine (5-HT) transporters (5-HTT), 5-HT(2A) and 5-HT(4) receptor expression in forebrain, and on neural cell adhesion molecule (NCAM) and 25-kDa synaptosomal associated protein (SNAP-25) concentrations when applied as indices for synaptic remodeling in forebrain, hippocampus, and entorhinal cortex. Male Wistar rats were exposed to 0, 400, or 800 ppm of aromatic (20 vol.% aromatic hydrocarbons) or dearomatized white spirit (catalytically hydrogenated white spirit) in the inhaled air for 6 h/day, 7 days/week for 3 weeks. The 5-HTT B(max) and K(d) were not affected. Both types of white spirit at 800 ppm decreased B(max) for the 5-HT(2A) receptor. The aromatic type decreased the K(d) of the 5-HT(2A) and 5-HT(4) receptors at 800 ppm. Aromatic white spirit did not affect NCAM or SNAP-25 concentrations or NCAM/SNAP-25 ratio in forebrain, whereas NCAM increased in hippocampus and the NCAM/SNAP-25 ratio decreased in entorhinal cortex. Dearomatized white spirit did not affect NCAM, SNAP-25, or NCAM/SNAP-25 ratio in any brain region. The affected 5-HT receptor expression and synaptic plasticity marker proteins indicate that inhalation exposure to high concentrations of white spirit may be neurotoxic to rats, especially the aromatic white spirit type.
Lam
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HR
Institute of Food Safety and Toxicology, Danish Veterinary and Food Administration, DK-2860 Søborg, Copenhagen, Denmark. hrl@fdir.dk
Plenge
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Jørgensen
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D000280:Administration, Inhalation; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002352:Carrier Proteins / Q000032:analysis; D018728:Entorhinal Cortex / Q000737:chemistry; D006624:Hippocampus / Q000737:chemistry; D006838:Hydrocarbons / Q000633:toxicity*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins / Q000032:analysis; D019006:Neural Cell Adhesion Molecules / Q000032:analysis; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044422:Receptors, Serotonin, 5-HT4; D050486:Serotonin Plasma Membrane Transport Proteins; D012997:Solvents / Q000633:toxicity*; D050825:Synaptosomal-Associated Protein 25
D002352:Carrier Proteins; D006838:Hydrocarbons; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; C494210:Snap25 protein, rat; D012997:Solvents; D050825:Synaptosomal-Associated Protein 25; D044422:Receptors, Serotonin, 5-HT4; C013089:ligroin