Differential effects of N-methyl-D-aspartic acid and L-homocysteic acid on cerebellar Purkinje neurons

The effects of N-methyl-D-aspartic acid (NMDA) and L-homocysteic acid (LH) were measured on cerebellar Purkinje neurons. In urethane-anesthetized rats, iontophoretic application of NMDA elicited 3 different effects on the spontaneous activity of Purkinje cells: excitation, inhibition and biphasic responses consisting of excitation followed by inhibition. On the other hand, LH elicited excitation, only, regardless of the actions of NMDA on the same neurons. We also examined the effects of various excitatory amino acid antagonists on NMDA- and LH-mediated responses. Excitatory effects of NMDA were antagonized effectively by D.L-2-amino-5-phosphonovalerate (APV), ketamine, gamma-D-glutamylglycine (DGG), D,L-2-amino-7-phosphonoheptanoate (APH), and were not influenced significantly by L-glutamate diethylester (GDEE). Inhibitory responses of NMDA were antagonized by APV, APH and ketamine. LH-mediated excitations were influenced significantly by DGG and ketamine whereas GDEE, APV and APH failed significantly to attenuate the effects of LH. Based on the differential actions of LH and NMDA and the selectivity of NMDA antagonists for NMDA rather than LH-mediated excitations, it appears that the major actions of LH may not be mediated through NMDA receptor sites, at least in the cerebellum.