Effects of 2,5-hexanedione alone and in combination with acetone on radial arm maze behavior, the "brain-swelling" reaction and synaptosomal functions.
A multidisciplinary study to investigate 2,5-hexanedione (2,5-HD)-induced CNS-neurotoxicity and its proposed potentiation by acetone (AC) was conducted. Neurobehavioral testing, estimation of the brain-swelling reaction, neuropathological and morphometric measurements as well as synaptosomal 5-hydroxytryptamine (5-HT) uptake were evaluated. Male Wistar rats were exposed through their drinking water, for seven weeks, either to 0.5% 2,5-HD alone or to 0.5% 2,5-HD in combination with 0.5% AC. This 2,5-HD dose is known to cause neurotoxicity in the peripheral nervous system. Exposed animals were compared to a control group that received tap water. Acquisition but not performance of spatial learning, as measured in the radial 8-arm maze, was significantly inhibited by the coexposure to 2,5-HD and AC. Brain weights of rats exposed to 2,5-HD alone and to 2,5-HD and AC in combination, were slightly, albeit significantly, reduced. Synaptosomal high-affinity 5-HT uptake rate and uptake capacity were significantly reduced by 2,5-HD alone and in combination with AC. The morphometric results are reported in a companion paper. In conclusion, the present findings indicate that 2,5-HD is a CNS-neurotoxicant. The hypothesis about AC potentiation of 2,5-HD CNS-neurotoxicity was supported.
Lam
H R
HR
Institute of Toxicology, National Food Agency, Søborg, Denmark.
Larsen
J J
JJ
Ladefoged
O
O
Møller
A
A
Strange
P
P
Arlien-Søborg
P
P
D000096:Acetone / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001693:Biological Transport, Active / Q000187:drug effects; D001929:Brain Edema / Q000139:chemically induced*; D006588:Hexanones / Q000008:administration & dosage / Q000633:toxicity*; D007858:Learning / Q000187:drug effects; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D006588:Hexanones; D000096:Acetone; D012701:Serotonin; C011269:2,5-hexanedione