Systemic administration of D-amphetamine induced a delayed production of nitric oxide in the striatum of rats.
Nitric oxide (NO) is a free-radical gas with a role in various signal transduction processes. In the CNS, NO acts as an important central nervous messenger, but in excess it may be neurotoxic. Chronic or high dose administration of D-amphetamine (AMPH) has been shown to induce striatal neurotoxicity in rodents and primates. In this study, we studied whether AMPH given systemically elicits NO formation in the striatum of rats and determined the relationship between NO formation and striatal DAergic terminal damage. Our results demonstrated that a single large dose administration of AMPH with desipramine elicited a delayed production of NO and concomitant long-term DA loss in the striatum. These phenomena were blocked by treatment with either the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) or the glutamate N-methyl-D-aspartate antagonist MK-801. It appears that AMPH-induced NO formation is critical for development of long-lasting DAergic terminal toxicity in the striatum of rats.
Lin
H C
HC
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, ROC.
Kang
B H
BH
Wong
C S
CS
Mao
S P
SP
Wan
F J
FJ
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D003891:Desipramine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000929:Antidepressive Agents, Tricyclic; D015259:Dopamine Agents; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D009569:Nitric Oxide; D016291:Dizocilpine Maleate; D003891:Desipramine; D003913:Dextroamphetamine; D019331:NG-Nitroarginine Methyl Ester; D004298:Dopamine