Changes in muscarinic (M1 and M2 subtypes) and phencyclidine receptor density in the rat brain following trimethyltin intoxication.
The main purpose of this study was to determine whether one or both of the muscarinic receptor subtypes (M1 and M2) contributed to the total cholinergic receptor loss found in trimethyltin (TMT) treated rats and to assess the effect of TMT on phencyclidine (PCP) receptor density in several regions of the rat brain. The distribution and changes in muscarinic (M1 and M2) receptor and PCP receptor sites were analysed by means of quantitative autoradiography using [3H]quinuclidinyl benzilate (QNB) and [3H] N-(1-(2-thienyl) cyclohexyl) 3,4-piperidine (TCP) respectively. The results demonstrate a TMT induced decrease in [3H]QNB binding in a large number of brain regions particularly the hippocampal formation, for both M1 and M2 muscarinic receptor subtypes. There is also a decrease in [3H]TCP binding in several brain regions. The effects of TMT on PCP receptors suggest that TMT induced damage is not restricted to the cholinergic system and that N-methyl-D-aspartate (NMDA) receptors are also affected.
O'Connell
A
A
Pharmacology Department, University College, Galway, Ireland.
Earley
B
B
Leonard
B E
BE
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D017478:Receptors, Phencyclidine / Q000187:drug effects* / Q000378:metabolism; D014298:Trimethyltin Compounds / Q000506:poisoning*
D011976:Receptors, Muscarinic; D017478:Receptors, Phencyclidine; D014298:Trimethyltin Compounds; C046488:trimethyltin