Boegman R J, Parent A
Department of Pharmacology and Toxicology, Queen's University, Kingston, Ont., Canada.
Brain Res. 1988 Jun 14;452(1-2):219-26. doi: 10.1016/0006-8993(88)90026-1.
The effect of excitatory amino acid antagonists on antagonist on neuropeptide Y (NPY) and cholinergic neurons in the striatum of the rat was studied by means of NPY immunocytochemistry, DFP histochemistry for acetylcholinesterase (AChE), and biochemical determinations of choline acetyltransferase (ChAT). Intrastriatal infusion of drugs revealed that striatal neurons containing NPY are more sensitive than cholinergic neurons to the neurotoxic actions of kainic acid (KA), quinolinic acid (QA) and L-glutamic acid (GA); all 3 compounds produced a marked loss of NPY neurons, but only a moderate decrease in the number of AChE neurons or ChAT activity. Co-injection experiments showed that the neurotoxicity of QA and GA, but not that of KA, can be antagonized by the specific N-methyl-D-aspartate (NMDA) receptor antagonist 3-((+/-)-2-(carboxypiperazine-4-yl))-propyl-1-phosphonic acid (CPP). Destruction of the glutamatergic corticostriatal projection by cerebral decortication protected striatal NPY and cholinergic neurons against KA neurotoxicity. These results indicate that striatal NPY and cholinergic neurons receive prominent cortical amino acid afferents, and that the neurotoxic effect of QA and GA on these neurons is mediated through NMDA receptors.
