D-amphetamine-induced depletion of energy and dopamine in the rat striatum is attenuated by nicotinamide pretreatment.
The present study examined the effects of nicotinamide on the D-amphetamine (AMPH)-induced dopamine (DA) depletion and energy metabolism change in the rat striatum. In chronic studies, co-administration of AMPH with desipramine, a drug that retards the metabolism of AMPH, (10 mg/kg, intraperitoneal [i.p.], respectively) caused a significant decrease of striatal DA content measured 7 days later. Pretreatment with nicotinamide (500 mg/kg, i.p.), the precursor molecule for the electron carrier molecule nicotinamide adenine dinucleotide (NAD), attenuated this effect of AMPH, whereas itself exerted no long-term effect on striatal DA content. In acute studies, a decrease in striatal adenosine triphospate/adenosine diphosphate (ATP/ADP) ratio was found 3 h after co-injection of AMPH and desipramine. However, nicotinamide pretreatment blocked the reduced striatal ATP/ADP ratio and resulted in a striking increase in striatal NAD content in AMPH-treated rats. Furthermore, nicotinamide was noted to increase striatal ATP/ADP ratio and NAD content in saline-treated rats. These findings suggest that nicotinamide protects against AMPH-induced DAergic neurotoxicity in the striatum of rats via energy supplement.
Wan
F J
FJ
Institute of Undersea and Hyperbaric Medicine, Taipei, Taiwan, Republic of China.
Lin
H C
HC
Kang
B H
BH
Tseng
C J
CJ
Tung
C S
CS
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects*; D008297:Male; D009243:NAD / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D009243:NAD; D009536:Niacinamide; D003913:Dextroamphetamine; D004298:Dopamine