GABAergic modulation of hippocampal glutamatergic neurons: an in vivo microdialysis study.
We have demonstrated the effects of activation of presynaptic gamma-aminobutyric acid (GABA) receptors on glutamate release using in vivo brain microdialysis. A dialysis probe inserted into the hippocampus CA2 area of freely moving rats was perfused with Ringers solution containing 100 mM potassium chloride (KCl) or 0.05 mM veratridine for 20 min. Extracellular concentrations of amino acids were monitored by measuring their levels in dialysates by high performance liquid chromatography (HPLC) fluorometry. Perfusion with depolarizing agents, such as KCl or veratridine, increased extracellular glutamate levels in the hippocampus. Pretreatment with 1 mM GABA, before perfusion with depolarizing agents, significantly suppressed the depolarizing agent-induced increase in glutamate levels. The GABA(B) receptor agonist baclofen (1 mM) also significantly inhibited the depolarizing agent-induced increase in glutamate levels, whereas the GABA(A) receptor agonist, muscimol, had no affect. Similarly, baclofen (0.5 mM) decreased the KCl (13.5 mM)-induced 45Ca(2+) influx into cortical synaptosomes to 57% of the level induced in the absence of baclofen. On the other hands, GABA did not affect the increases in glycine and taurine level by depolarizing agents. These results suggest that GABA modulates depolarization-evoked glutamate release in the hippocampus by inhibiting Ca(2+) entry into neurons, an effect mediated by presynaptic GABA(B) receptors.
Tanaka
Sachiko
S
Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Tokyo Shinagawa 142-8555, Japan. stanaka@pharm.showa-u.ac.jp
Tsuchida
Akihiro
A
Kiuchi
Yuji
Y
Oguchi
Katsuji
K
Numazawa
Satoshi
S
Yoshida
Takemi
T
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D005998:Glycine / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D017551:Microdialysis; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D018079:Receptors, GABA / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013654:Taurine / Q000378:metabolism; D013997:Time Factors; D014701:Veratridine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D002121:Calcium Channel Blockers; D018755:GABA Agonists; D018079:Receptors, GABA; D013654:Taurine; D009118:Muscimol; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D011189:Potassium Chloride; D014701:Veratridine; D001418:Baclofen; D002118:Calcium; D005998:Glycine