Protection from kainic acid neuropathological syndrome by NMDA receptor antagonists: effect of MK-801 and CGP 39551 on neurotransmitter and glial markers.
Systemic administration of kainic acid results in the development of a characteristic convulsive syndrome, accompanied by neuropathological alterations and loss of transmitter markers in some forebrain regions. Since some of these effects appear to involve the N-methyl-D-aspartate (NMDA) subtype of excitatory amino acid receptors, the protection given by a non-competitive (MK-801) and a competitive (CGP 39551) NMDA receptor antagonist against the loss of glutamatergic and gamma-amino butyric acid (GABAergic) neurochemical markers was compared. Appropriate doses of both compounds (1 mg/kg MK-801 and 25 mg/kg CGP 39551) completely reversed the decrease of high affinity uptake of glutamate and activity of glutamate decarboxylase in the olfactory cortex, amygdala, hippocampus and lateral septum. In addition, they also essentially counteracted the increase of a glial marker, the enzyme glutamine synthetase, consequent to neuronal degeneration. The results confirmed that involvement of NMDA receptors is essential for the full expression of neuropathological effects of kainic acid. They also support the use of a competitive antagonist of the NMDA receptor, such as CGP 39551, to afford substantial protection against the excitotoxic damage, whilst giving fewer side effects and motor disturbances than MK-801.
Department of Biology, University of Bologna, Italy.
M
M
Virgili
P
P
Migani
A
A
Contestabile
O
O
Barnabei
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004827:Epilepsy / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007608:Kainic Acid / Q000037:antagonists & inhibitors*; D008297:Male; D009457:Neuroglia / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013577:Syndrome
D018377:Neurotransmitter Agents; D016194:Receptors, N-Methyl-D-Aspartate; C064540:CGP 39551; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D007608:Kainic Acid