Monitoring nitric oxide (NO) in rat locus coeruleus: differential effects of NO synthase inhibitors.
A porphyrinic microsensor combined with in vivo voltammetry was used to monitor extracellular nitric oxide (NO) in the locus coeruleus (LC) of anaesthetized rats. Administration of N omega-nitro-L-arginine p-nitro-anilide (100 mg/kg, i.p) or 7-nitro indazole (30 mg/kg, i.p.), which both inhibit preferentially neuronal NO synthase (NOS), induced a marked decrease in the NO oxidation peak height. On the other hand, N omega-nitro-L-arginine methyl ester (L-NAME) (200 mg/kg, i.p.), a less selective NOS inhibitor, failed to decrease the NO signal. Moreover, intra LC administration of NMDA, known to activate LC noradrenergic neurones, increased the NO signal. This study demonstrates the usefulness of in vivo voltammetry to monitor basal levels of NO and their changes in the LC. Differential effects of NOS inhibitors show that their central activity need to be assessed through in situ measurement of NO before using these inhibitors as neuropharmacological tools.
Desvignes
C
C
Laboratoire de Neuropharmacologie et Neurochimie (INSERM CJF 95-06), Faculté de Pharmacie, Lyon, France.
Robert
F
F
Vachette
C
C
Chouvet
G
G
Cespuglio
R
R
Renaud
B
B
Lambás-Señas
L
L
D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004563:Electrochemistry; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007191:Indazoles / Q000494:pharmacology; D008125:Locus Coeruleus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008991:Monitoring, Physiologic / Q000379:methods*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000032:analysis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000813:Anilides; D004791:Enzyme Inhibitors; D007191:Indazoles; D009569:Nitric Oxide; C080840:N(G)-nitroarginine-4-nitroanilide; D001120:Arginine; D019001:Nitric Oxide Synthase; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester