A. Moralesvillagran et R. Tapia, PREFERENTIAL STIMULATION OF GLUTAMATE RELEASE BY 4-AMINOPYRIDINE IN RAT STRIATUM IN-VIVO, Neurochemistry international, 28(1), 1996, pp. 35-40
The potassium channel blocker 4-aminopyridine (4-AP) is a potent convu
lsant drug which, in vitro, stimulates the release of neurotransmitter
amino acids. We have studied the effect of 4-AP in vivo on the extrac
ellular concentration of amino acids in rat striatum, by means of micr
odialysis and HPLC. Perfusion with 4-AP in the awake animal produced i
ntense motor alterations, including barrel turning and running fits. T
herefore, most microdialysis experiments were carried out in anestheti
zed rats. Perfusion with 20-75 mM 4-AP for 12.5 min resulted in a mass
ive increase in extracellular glutamate (up to 20-fold), smaller incre
ases in aspartate and taurine (up to 10-fold) and slight increments in
glutamine, alanine, glycine and GABA. In contrast, perfusion with 100
mM K+ produced, mainly, an increment in taurine (7-fold) and modest i
ncreases in glutamate and aspartate (100-300%), as well as a notable d
ecrease in glutamine. Tetraethylammonium (TEA, 120 mM) perfusion induc
ed taurine and glutamate elevations similar to those after high K+, bu
t glutamine was not affected. In unanesthetized rats, perfusion with 4
0 mM 4-AP induced changes in extracellular amino acids similar to thos
e observed under anesthesia. In these animals neither high K+ nor TEA
affected significantly the motor behavior. The results suggest that an
enhancement of glutamatergic synaptic transmission, rather than a gen
eral depolarizing action, is an important factor in the neuronal hyper
excitability induced by 4-AP, which is consistent with the previously
demonstrated inhibition of its convulsant effect by glutamate receptor
antagonists.