Behavioural, biochemical and histological effects of trimethyltin (TMT) induced brain damage in the rat.
To assess the nature and extent of behavioural, biochemical and histological changes induced by trimethyltin (TMT), rats were treated with a single injection of TMT over a dose range of 6, 7 and 8 mg/kg i.p. Behavioural observations were performed at a minimum of 21 days after the administration of TMT. The behavioural consequences of TMT were hyperactivity in the open-field test, increased locomotor activity and deficits in passive and active avoidance behaviour, T-maze alternation and Morris Water Maze behaviour. The behavioural changes were dose dependent and were accompanied by a degree of pathological damage to the hippocampal pyramidal cells which was particularly apparent at the highest dose. The main biochemical effects of TMT involved deficits in the serotonergic and GABA-ergic systems and a decrease in M1 and M2 binding sites in the hippocampus. These results suggest that the toxic interaction of TMT with the hippocampus and other limbic brain regions may be responsible for its effect on learning and memory.
Earley
B
B
Pharmacology Department, University College, Galway, Ireland.
Burke
M
M
Leonard
B E
BE
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001362:Avoidance Learning / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001925:Brain Damage, Chronic / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000097:blood; D007980:Levodopa / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D009928:Organ Specificity; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D012016:Reference Values; D012701:Serotonin / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects*; D014298:Trimethyltin Compounds / Q000633:toxicity*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018377:Neurotransmitter Agents; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D014298:Trimethyltin Compounds; C046488:trimethyltin; D012701:Serotonin; D007980:Levodopa; D006897:Hydroxyindoleacetic Acid; D005680:gamma-Aminobutyric Acid; D011813:Quinuclidinyl Benzilate; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D004298:Dopamine; D009638:Norepinephrine