| Title | Modulation of dopaminergic neurotransmission in rat striatum upon in vitro and in vivo diclofenac treatment. | | Author(s) | Milusheva E, Baranyi M, Kittel A, Fekete A, Zelles T, Vizi ES, Sperlágh B | | Institution | Institute of Neurobiology (former Institute of Physiology), Bulgarian Academy of Sciences, Acad. G. Bonchev str., Bl. 23, 1113 Sofia, Bulgaria. | | Source | J Neurochem 2007 Nov 25. | | Abstract | Diclofenac is a widely used non-steroidal anti-inflammatory drug, which also act as a mitochondrial toxin. Since it is known that selective mitochondrial complex I inhibition combined with mild oxidative stress causes striatal dopaminergic dysfunction, we tested whether diclofenac also compromise dopaminergic function in the striatum. [(3)H]Dopamine release was measured from rat striatal slices after in vitro (2 hours; 10-25 muM) or in vivo (3 mg/kg i.v. for 28 days) diclofenac treatment. In vitro treatment significantly decreased [(3)H]dopamine uptake and dopamine content of the slices. H(2)O(2) (0.1 mM)-evoked dopamine release was enhanced. Intracellular ROS production was not significantly changed in the presence of diclofenac. After in vivo diclofenac treatment no apparent decrease in striatal dopamine content was observed and the uptake of [(3)H]dopamine 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 H(2)O(2)-evoked [(3)H]dopamine release was significantly decreased and the effluent contained a significant amount of [(3)H]octopamine, [(3)H]tyramine and [(3)H]beta-phenylethylamine. The ATP content and adenylate energy charge were decreased. In conclusion, whereas in vitro diclofenac pre-treatment resembles the effect of the mitochondrial toxin rotenone, in vivo it rather counteracts than aggravates dopaminergic dysfunction. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 18036194 |
|
