NO synthase inhibitors attenuate locus coeruleus catecholamine metabolism and behavior induced by morphine withdrawal.
The effects of nitric oxide synthase (NOS) inhibitors were examined simultaneously on the behavior and on the catecholaminergic metabolism in the locus coeruleus (LC) during morphine withdrawal using microdialysis in freely moving rats. Morphine withdrawal was precipitated by naltrexone administration to morphine-treated rats. Acute pretreatment of rats with NOmicron-nitro-L-arginine-p-nitroanilide (L-NAPNA) or 7-nitroindazole (7-NI) before naltrexone challenge attenuated the behavioral expression of morphine withdrawal and strongly reduced the withdrawal-induced increase in 3,4-dihydroxyphenylacetic acid (DOPAC) in the LC. The two NOS inhibitors also decreased DOPAC in absence of naltrexone challenge. These results suggest a role for NO in the expression of morphine withdrawal syndrome that may be mediated, at least in part, by LC noradrenergic neurons.
Javelle
Nathalie
N
Laboratoire de Neuropharmacologie et Neurochimie, Faculté de Pharmacie, INSERM U512, Université Claude Bernard, 8 Avenue Rockefeller, 69373 Lyon Cedex 08, France.
Bérod
Anne
A
Renaud
Bernard
B
Lambás-Señas
Laura
L
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002395:Catecholamines / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008125:Locus Coeruleus / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009294:Narcotics / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000201:enzymology*
D002395:Catecholamines; D004791:Enzyme Inhibitors; D009294:Narcotics; D015102:3,4-Dihydroxyphenylacetic Acid; D009020:Morphine; D019001:Nitric Oxide Synthase