Details

Autor(en) / Beteiligte

• Dı&#x0301
• az-Véliz, Gabriela
• Mora, Sergio
• Gómez, Patricia
• Dossi, Ma Teresa
• Montiel, Juan
• Arriagada, Christian
• Aboitiz, Francisco
• Segura-Aguilar, Juan

Titel

Behavioral effects of manganese injected in the rat substantia nigra are potentiated by dicumarol, a DT-diaphorase inhibitor

Ist Teil von

• Pharmacology, biochemistry and behavior, 2004-02, Vol.77 (2), p.245-251

Ort / Verlag

New York, NY: Elsevier Inc

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• The purpose of this study was to evaluate the contribution of DT-diaphorase inhibition to in vivo neurodegenerative effects of dopamine (DA) oxidation to the corresponding o-quinones. The neurotoxicity to nigrostriatal DA neurons was induced by injection of manganese pyrophosphate (Mn 3+) complex as a prooxidizing agent alone or together with the DT-diaphorase inhibitor dicumarol into the right rat substantia nigra. The behavioral effects were compared with those induced after selective lesions of dopaminergic neurons with 6-hydroxydopamine (6-OHDA). Intranigral injection of Mn 3+ and Mn 3+ plus dicumarol produced significant impairment in motor behavior compared with control animals. However, the effect seen in the Mn 3+ plus dicumarol injected group was significantly more severe than that observed in the Mn 3+ alone injected group. In motor activity and rearing behavior, the simultaneous injection of Mn 3+ plus dicumarol produced a 6-OHDA-like impairment. Similar effects were observed in the acquisition of a conditioned avoidance response (CAR). Dicumarol significantly impaired avoidance conditioning although without affecting the motor behavior. The behavioral effects were correlated to the extent of striatal tyrosine hydroxylase (TH)-positive fiber loss. Rats receiving unilateral intranigral Mn 3+ and Mn 3+ plus dicumarol injections exhibited a significant reduction in nigrostriatal TH-positive fiber density in medial forebrain bundle compared with the contralateral noninjected side. In conclusion, this study provides evidence that the neurotoxicity of Mn 3+ in vivo is potentiated by DT-diaphorase inhibition, suggesting that this enzyme could play a neuroprotective role in the nigrostriatal DA systems.