A microdialysis study of amino acid concentrations in the extracellular fluid of the substantia nigra of freely behaving GEPR-9s: relationship to seizure predisposition.
Substantia nigra (SN) is known to play an important role in seizure generalization. Both excitatory and inhibitory neurotransmitters can modulate this role of SN. Previous studies have shown that GABA as well as aspartate and glutamate participate in seizure regulation through this site. Evidence for such a role comes from studies on the genetically epilepsy-prone rat (GEPR) and other seizure models. In the GEPR, bilateral microinjections of NMDA receptor antagonists in SN block or reduce seizure severity. In order to further evaluate which neurotransmitters are specifically involved at the SN level of seizure regulation in the GEPR, we undertook a microdialysis study of K+ stimulated release of amino acids in the SN of GEPR-9s- and non-epileptic controls. A 1 mm loop-type microdialysis probe was inserted through pre-implanted guides into the SN of awake and freely moving rats (seven GEPR-9s and four non-epileptic controls), and used to perfuse a 100 mM K+ (high K+) solution for 2 h. Four 30 microliters samples were collected prior to high K+ stimulation (basal release), during high K+ perfusion, and after high K+ infusion. After precolumn derivatization with phenylisothiocyanate, levels of aspartic (ASP) and glutamic (GLU) acids, glycine (GLY), taurine (TAU) and GABA were measured by reversed phase high performance liquid chromatography. Two hours after the initiation of high K+ infusion, the increases relative to basal were, for non-epileptic controls, 35%, 74%, 68%, 847% and 283% respectively for ASP, GLU, GLY, TAU and GABA. Corresponding increases for GEPR-9s were 14%, 10%, 41%, 505% and 123% respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Doretto
M C
MC
Physiology Department, Ribeirao Preto School of Medicine, University of Sao Paulo, Brazil.
Burger
R L
RL
Mishra
P K
PK
Garcia-Cairasco
N
N
Dailey
J W
JW
Jobe
P C
PC
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004827:Epilepsy / Q000235:genetics / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000503:physiopathology*; D013056:Spectrophotometry, Ultraviolet; D013378:Substantia Nigra / Q000033:anatomy & histology / Q000378:metabolism*; D013654:Taurine / Q000378:metabolism
D000596:Amino Acids; D013654:Taurine; D011188:Potassium