Modulation of dopaminergic neurotransmission in rat striatum upon in vitro and in vivo diclofenac treatment.
Diclofenac (DCF) is a widely used non-steroidal anti-inflammatory drug, which also act as a mitochondrial toxin. As it is known that selective mitochondrial complex I inhibition combined with mild oxidative stress causes striatal dopaminergic dysfunction, we tested whether DCF also compromise dopaminergic function in the striatum. [3H]Dopamine ([3H]DA) release was measured from rat striatal slices after in vitro (2 h, 10-25 micromol/L) or in vivo (3 mg/kg i.v. for 28 days) DCF treatment. In vitro treatment significantly decreased [3H]DA uptake and dopamine (DA) content of the slices. H2O2 (0.1 mmol/L)-evoked DA release was enhanced. Intracellular reactive oxygen species production was not significantly changed in the presence of DCF. After in vivo DCF treatment no apparent decrease in striatal DA content was observed and the uptake of [3H]DA into slices was increased. The intensity of tyrosine hydroxylase immunoreactivity in the striatum was highly variable, and both decrease and increase were observed in individual rats. The H2O2-evoked [3H]DA release was significantly decreased and the effluent contained a significant amount of [3H]octopamine, [3H]tyramine, and [3H]beta-phenylethylamine. The ATP content and adenylate energy charge were decreased. In conclusion, whereas in vitro DCF pre-treatment resembles the effect of the mitochondrial toxin rotenone, in vivo it rather counteracts than aggravates dopaminergic dysfunction.
Institute of Neurobiology (former Institute of Physiology), Bulgarian Academy of Sciences, Sofia, Bulgaria.
Elisaveta
E
Milusheva
Mária
M
Baranyi
Agnes
A
Kittel
Adam
A
Fekete
Tibor
T
Zelles
E Sylvester
ES
Vizi
Beáta
B
Sperlágh
D000255:Adenosine Triphosphate / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009655:Octopamine / Q000378:metabolism; D010624:Phenelzine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D014316:Tritium / Q000378:metabolism; D014439:Tyramine / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D016861:Cyclooxygenase Inhibitors; D017382:Reactive Oxygen Species; D014316:Tritium; D004008:Diclofenac; D009655:Octopamine; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D014446:Tyrosine 3-Monooxygenase; D010624:Phenelzine; D004298:Dopamine; D014439:Tyramine