The effect of acute kainic acid treatment on dopamine D2 receptors in rat brain.
Acute exposure to kainic acid (KA) induces neurochemical changes in dopaminergic systems in the brain and the aim of the present study was to investigate the acute toxicity of KA upon dopamine D2 receptors. Adult rats were injected intraperitoneally with either saline or 16 mg/kg KA. Brains were removed after 4 h. Membrane homogenates were prepared from seven brain regions and in addition, frozen coronal sections were sectioned for comparative quantitative autoradiographic analysis. Dopamine D2 receptors were characterised by saturation studies using [125I]iodosulpiride, [3H]raclopride and [3H]spiperone. KA produced a 2-fold decrease in receptor affinity for [125I]iodosulpiride and a 2-fold increase in receptor density in all regions studied except striatum. Quantitative autoradiography with [125I]iodosulpiride showed similar increases in D2 labelling following KA except in caudate putamen, nucleus accumbens and olfactory tubercle. In contrast, there was no change in [3H]spiperone binding in whole brain minus striatum nor in striatum alone after KA treatment. KA produced a significant increase in Bmax for [3H]raclopride in whole brain minus striatum and in striatum alone with minimal changes in affinity. These findings demonstrate acute changes in rat brain dopamine D2 receptors labelled with [125I]iodosulpiride and [3H]raclopride but not [3H]spiperone after KA treatment predominantly in extra striatal regions.
Ridd
M J
MJ
Receptors and Cellular Regulation Research Group, School of Biological Sciences, University of Surrey, Guildford, UK.
Kitchen
I
I
Fosbraey
P
P
D000818:Animals; D001921:Brain / Q000187:drug effects*; D007457:Iodine Radioisotopes / Q000378:metabolism; D007553:Isotope Labeling; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D020891:Raclopride; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism; D012457:Salicylamides / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism; D013469:Sulpiride / Q000031:analogs & derivatives / Q000378:metabolism; D014316:Tritium / Q000378:metabolism
D007457:Iodine Radioisotopes; D017448:Receptors, Dopamine D2; D012457:Salicylamides; C045105:iodosulpride; D014316:Tritium; D020891:Raclopride; D013134:Spiperone; D013469:Sulpiride; D007608:Kainic Acid