Systemic administration of cocaine, given alone or in combination with sensory stimuli, differentially affects L-arginine-nitric oxide metabolism in discrete regions of the brain of rat.
The effect of cocaine on brain regional metabolism of L-arginine to nitric oxide (NO) has been studied in rat by measuring the level of citrulline, the co-product of NO synthesis, using a HPLC based methodology. A single i.p. administration of 1 mg/kg cocaine, and a daily treatment for up to 5 consecutive days, failed to affect significantly citrulline content in the striatum, hippocampus and cortex. By contrast, in these regions of the brain a single or 5-day repeated higher dose of cocaine (10 mg/kg, i.p.) caused a significant increase in the co-product of NO synthesis and this has been abolished in a stereoselective fashion by L-NAME (10 mg/kg i.p. given 30 min before). Under cocaine high dose treatment, 1 h acoustic stimulation, which per se resulted ineffective, enhanced stimulant-induced increases in citrulline content seen in the striatum and abolished the increase of this amino acid observed in the hippocampus and cortex both after single or 5-day repeated injection of cocaine. In conclusion, these data demonstrate that cocaine stimulates the conversion of L-arginine to NO in the brain of rat and this is affected by concomitant exposure to acoustic stimulation.
Bagetta
G
G
Department of Pharmaco-Biology, University of Calabria, Italy.
Rodinò
P
P
Arabia
A
A
Massoud
R
R
Paoletti
A M
AM
Nisticò
R
R
Passantino
L
L
Preziosi
P
P
D000161:Acoustic Stimulation; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001931:Brain Mapping; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D002956:Citrulline / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects; D004334:Drug Administration Schedule; D005625:Frontal Lobe / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
D000697:Central Nervous System Stimulants; D002956:Citrulline; D009569:Nitric Oxide; D001120:Arginine; D003042:Cocaine