Norepinephrine loss selectively enhances chronic nigrostriatal dopamine depletion in mice and rats.
In this study we investigated whether a selective pattern of norepinephrine loss potentiates methamphetamine-induced striatal dopamine depletion in rats. We also evaluated whether chronic norepinephrine depletion reduces the threshold dose of methamphetamine necessary to induce long-lasting striatal dopamine loss in mice and in rats. Pre-treatment with the selective noradrenergic neurotoxin DSP-4 (50 mg/kg, i.p.) in mice and in rats significantly enhanced methamphetamine-induced striatal dopamine depletion. Administration of a low dose of methamphetamine (1 x 5 mg/kg and 3 x 5 mg/kg, respectively, i.p., at 2-h interval) to C57B1/6N mice and Sprague-Dawley rats did not decrease striatal dopamine levels when injected alone but produced a significant decrease in striatal dopamine when given to rodents carrying a long-lasting norepinephrine depletion previously induced by DSP-4. Our results suggest that norepinephrine loss might both enhance neurotoxic damage and decrease the threshold for neurotoxicity to nigrostriatal dopaminergic neurons in different animal species.
Fornai
F
F
Institute of Pharmacology, School of Medicine, University of Pisa, Rome, Italy.
Torracca
M T
MT
Bassi
L
L
D'Errigo
D A
DA
Scalori
V
V
Corsini
G U
GU
D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000378:metabolism*; D013997:Time Factors
D018663:Adrenergic Agents; D001596:Benzylamines; C012102:DSP 4; D004298:Dopamine; D009638:Norepinephrine