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.
Institute of Pharmacology, School of Medicine, University of Pisa, Rome, Italy.
F
F
Fornai
M T
MT
Torracca
L
L
Bassi
D A
DA
D'Errigo
V
V
Scalori
G U
GU
Corsini
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