Tetanus toxin-induced effects on extracellular amino acid levels in rat hippocampus: an in vivo microdialysis study.
Tetanus toxin is a potent neurotoxin that is widely considered to produce its effect through impairment of inhibitory neurotransmission. We report the effect of a single unilateral intrahippocampal injection of tetanus toxin on extracellular levels of neuroactive amino acids in freely moving rats, at times ranging between 1 and 7 days posttreatment. Tetanus toxin treatment did not alter extracellular levels of aspartate, glutamate, and taurine at any time during the study. However, although extracellular GABA levels were unaffected by toxin injection 1, 2, and 3 days after treatment, they were reduced (45 +/- 8% of contralateral vehicle-injected level) at day 7. Challenge with a high K+ concentration, 7 days after treatment, produced elevations in extracellular levels of taurine and GABA in both vehicle- and toxin-injected hippocampi, with evoked levels of GABA being lower in the toxin-treated side (39 +/- 16% of contralateral vehicle-injected level). Aspartate and glutamate levels were not increased by high-K+ infusion. These findings are discussed in relation to the possible role that an imbalance in excitatory/inhibitory tone may play in the production of tetanus toxin-induced neurodegeneration.
Britton
P
P
Department of Pharmacology, School of Pharmacy, London, England.
Whitton
P S
PS
Fowler
L J
LJ
Bowery
N G
NG
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005110:Extracellular Space / Q000737:chemistry*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D008845:Microinjections; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013744:Tetanus Toxin / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000596:Amino Acids; D013744:Tetanus Toxin; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D011188:Potassium