Amphetamine causes dopamine depletion and cell death in the mouse olfactory bulb.
Amphetamine is a neurotoxic psychostimulant that causes dopamine depletion and neuronal death in the rodent striatum. In the present study, we sought to determine if toxic doses of the drug can also induce pathological changes in the mouse olfactory bulb. We found that injections of amphetamine (10 mg/kg x 4, given 2 h apart) caused significant decreases in dopamine levels in that structure. This dose of the drug also induced substantial increases in the number of terminal deoxynucleotidyl transferase-mediated deoxyribonucleotide triphosphate (dNTP) nick end labeling (TUNEL)-positive cells in the olfactory bulb indicative of elevated DNA fragmentation. These results show that the toxic effects of amphetamine involve the olfactory bulb in addition to the striatum. These observations need to be taken into consideration when discussing the clinical course of amphetamine addiction.
Molecular Neuropsychiatry Branch, National Institute on Drug Abuse, Intramural Research Program, NIH/DHHS, Baltimore, MD 21224, USA.
Fidelis E
FE
Atianjoh
Bruce
B
Ladenheim
Irina N
IN
Krasnova
Jean Lud
JL
Cadet
D000661:Amphetamine / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000633:toxicity*; D053938:DNA Fragmentation; D004298:Dopamine / Q000378:metabolism*; D015536:Down-Regulation; D004334:Drug Administration Schedule; D020287:In Situ Nick-End Labeling; D007267:Injections; D008297:Male; D051379:Mice; D009830:Olfactory Bulb / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
D000697:Central Nervous System Stimulants; D000661:Amphetamine; D004298:Dopamine