Soluble amyloid beta1-42 reduces dopamine levels in rat prefrontal cortex: relationship to nitric oxide.
Several studies suggest a pivotal role of amyloid beta (Abeta)(1-42) and nitric oxide (NO) in the pathogenesis of Alzheimer's disease. NO also possess central neuromodulatory properties. To study the soluble Abeta(1-42) effects on dopamine concentrations in rat prefrontal cortex, microdialysis technique was used. We showed that i.c.v. injection or retrodialysis Abeta(1-42) administration reduced basal and K(+)-stimulated dopamine levels, measured 2 and 48 h after peptide administration. Immunofluorescent experiments revealed that after 48 h from i.c.v. injection Abeta(1-42) was no longer detectable in the ventricular space. We then evaluated the role of NO on Abeta(1-42)-induced reduction in dopamine concentrations. Subchronic L-arginine administration decreased basal dopamine levels, measured either 2 h after i.c.v. Abeta(1-42) or on day 2 post-injection, whereas subchronic 7-nitroindazole administration increased basal dopamine concentrations, measured 2 h after i.c.v. Abeta(1-42) injection, and decreased them when measured on day 2 post-Abeta(1-42)-injection. No dopaminergic response activity was observed after K(+) stimulation in all groups. These results suggest that the dopaminergic system seems to be acutely vulnerable to soluble Abeta(1-42) effects. Finally, the opposite role of NO occurring at different phases might be regarded as a possible link between Abeta(1-42)-induced effects and dopaminergic dysfunction.
Trabace
L
L
Department of Biomedical Sciences, University of Foggia, Foggia, Italy. trabace@unifg.it
Kendrick
K M
KM
Castrignanò
S
S
Colaianna
M
M
De Giorgi
A
A
Schiavone
S
S
Lanni
C
C
Cuomo
V
V
Govoni
S
S
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D017551:Microdialysis / Q000379:methods; D009569:Nitric Oxide / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D007191:Indazoles; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D009569:Nitric Oxide; D001120:Arginine; C080122:7-nitroindazole; D004298:Dopamine