Selective behavioural impairment after acute intoxication with trimethyltin (TMT) in rats.
A series of experiments was conducted to characterize the long term behavioural consequences of acute intoxication with trimethyltin (TMT) (5,6,7, mg/kg p.o.). The acute toxicity syndrome, including weight loss, convulsions, irritability and hyper-reactivity was confirmed in treated rats. These symptoms subsided to reveal marked increases in locomotor activity in a novel environment but no lasting effects on consummatory behaviour or sensorimotor integration. Neither two-way active avoidance nor passive avoidance learning were impaired by doses of up to 7 mg/kg p.o. although intertrial activity was elevated in the shuttle box and extinction responding was increased. Place navigation in a water maze was impaired, particularly at the highest dose of TMT (7 mg/kg p.o.) and when a brief training phase (8 trials) was used. Finally, TMT lesioned rats were compared with controls on spatial and non-spatial discrimination tasks. Following 7 mg/kg p.o. TMT rats were highly impaired on the spatial discrimination but not the non-spatial discrimination despite the greater difficulty of the latter task. Histological studies confirmed the pathological effects of TMT in limbic structures, particularly the pyramidal cells of CA1 and CA4, and also revealed increased acetylcholinesterase activity within the molecular layer of the dentate gyrus. The selective, long term behavioural impairments caused by TMT are discussed in the light of their qualitative similarity to the effects of hippocampectomy or hippocampal denervation. TMT lesioned rats may provide a suitable functional model for the partial hippocampal and temporal lobe pathology characteristic of Alzheimer's disease.
Hagan
J J
JJ
Scientific Development Group, Organon International B.V., Oss, The Netherlands.
Jansen
J H
JH
Broekkamp
C L
CL
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002940:Circadian Rhythm / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014220:Trialkyltin Compounds / Q000633:toxicity*; D014298:Trimethyltin Compounds / Q000633:toxicity*
D014220:Trialkyltin Compounds; D014298:Trimethyltin Compounds; C046488:trimethyltin