Fj. Wan et al., D-amphetamine-induced depletion of energy and dopamine in the rat striatumis attenuated by nicotinamide pretreatment, BRAIN RES B, 50(3), 1999, pp. 167-171
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 desiprami
ne, 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.), th
e 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 i
n 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 HAD 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 ener
gy supplement. (C) 1999 Elsevier Science Inc.