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, th e 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 conse cutive days, failed to affect significantly citrulline content in the stria tum, hippocampus and cortex. By contrast, in these regions of the brain a s ingle or 5-day repeated higher dose of cocaine (10 mg/kg, i.p.) caused a si gnificant increase in the co-product of NO synthesis and this has been abol ished in a stereoselective fashion by L-NAME (10 mg/kg i.p. given 30 min be fore). Under cocaine high dose treatment, 1 h acoustic stimulation, which p er se resulted ineffective, enhanced stimulant-induced increases in citrull ine content seen in the striatum and abolished the increase of this amino a cid observed ire the hippocampus and cortex both after single or 5-day repe ated injection of cocaine. In conclusion, these data demonstrate that cocai ne stimulates the conversion of L-arginine to NO in the brain of rat and th is is affected lay concomitant exposure to acoustic stimulation. (C) 1999 E lsevier Science Ireland Ltd. All rights reserved.