Origin of extracellular dopamine increase induced by lactic acid striatal perfusion monitored by microdialysis in the awake rat.
In previous studies we showed that a striatal lactic acid perfusion-induced lactacidosis produces a diphasic increase in extracellular dopamine (DA). In the present study, different pharmacological reagents were used to determine the origin of accumulated DA. Our data show that both DA accumulations were totally suppressed by tetrodotoxin and nicardipine, indicating a relationship with membrane depolarization and a Ca(2+)-dependent effect. The first DA peak was largely reduced by a specific inhibitor of DA uptake such as GBR-12935, and the second was totally suppressed by tyramine and reserpine and lowered and delayed by GBR-12935. These results compared to data in the literature suggest that the first increase in extracellular DA resulted mainly from a release of cytosolic DA by reversal of the DA transporter, while the second was mainly due to a release of vesicular DA by exocytosis. These data indicate that lactic acid perfusion helps clarify the mechanisms involved in this process and could be useful for the study of new treatments against the hyperactive dopaminergic reaction occuring during ischemia.
Remblier
C
C
Centre d'Etudes et de Recherche sur les Xénobiotiques (UPRES EA 1223), Faculté de Médecine et de Pharmacie, Poitiers, France.
Pontcharraud
R
R
Vandel
B
B
Piriou
A
A
Huguet
F
F
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D019344:Lactic Acid / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009529:Nicardipine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D014439:Tyramine / Q000494:pharmacology; D014851:Wakefulness
D018759:Adrenergic Uptake Inhibitors; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D010879:Piperazines; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D019344:Lactic Acid; D013779:Tetrodotoxin; D012110:Reserpine; C044630:1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine; D009529:Nicardipine; D004298:Dopamine; D014439:Tyramine