Long lasting behavioral effects of dimethyl sulfoxide and the "peripheral" toxicant p-bromophenylacetylurea.
Behavioral toxic effects caused by a relatively small dose of the "peripheral" neurotoxin, p-bromophenylacetylurea (BPAU), and of its vehicle, dimethyl sulfoxide (DMSO) were investigated. BPAU induces, in rats, a central-peripheral distal axonopathy similar to that produced in humans by toxic organophosphorus-containing compounds, and has been proposed as a model to study this type of toxicity in a convenient experimental mammal. Rats were injected with BPAU (50 or 100 mg/kg) in DMSO (1 ml/kg), with DMSO alone, or with saline. 100 mg BPAU/kg produced permanent weight loss and hind limb paresis; the low dose did not. Behavioral testing, 2 days to 4 mo post-treatment, indicated that DMSO and/or 50 mg/kg of BPAU retarded habituation of spontaneous exploratory activity, impaired acquisition of conditioned (auto-shaped) behavior, and changed the dose-response relationship ford-amphetamine-induced suppression of operant (fixed ratio 32) responding. BPAU-treated animals were also impaired in initial performance of operant behavior maintained by a fixed ratio schedule of reinforcement, at high (greater than or equal to FR 16) ratio values. Thus, neurobehavioral toxicity may occur at doses too low to induce organophosphorus-type sensorimotor impairment or pathology. Further, DMSO may also exert effects on neurobehavioral function, suggesting it too may be potentially toxic within this domain.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D003913:Dextroamphetamine / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000633:toxicity*; D005508:Food Deprivation; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010243:Paralysis / Q000139:chemically induced; D051381:Rats; D011919:Rats, Inbred Strains; D012055:Reinforcement Schedule; D013997:Time Factors; D014508:Urea / Q000031:analogs & derivatives* / Q000633:toxicity
C004506:4-bromophenylacetylurea; D014508:Urea; D003913:Dextroamphetamine; D004121:Dimethyl Sulfoxide