Correlation between brain nitric oxide synthase activity and opiate withdrawal.
The opiate withdrawal induced by administration of naloxone to morphine-dependent mice correlates with an increment of calcium- dependent nitric oxide synthase (NOS) activity in the cerebellum. L-NAME, an irreversible competitive inhibitor of NOS (0.5, 5, 25, 50 mg/kg) injected sc. 45 min. prior to naloxone significantly reduced the number of escape jumps and other motor symptoms of abstinence. In addition, L-NAME also decreased NOS activity in cerebellum. L-arginine, but not D-arginine, when coadministered with L-NAME, prevented both the inhibition of NOS activity and the reduction of withdrawal symptoms induced by L-NAME in morphine-withdrawn animals. These results demonstrate a hyperactivity of the L-arginine: NO pathway in opiate withdrawal and suggests the possibility of a therapeutic use of NOS inhibitors in this state.
Leza
J C
JC
Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense de Madrid, Spain.
Lizasoain
I
I
Cuéllar
B
B
Moro
M A
MA
Lorenzo
P
P
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D002531:Cerebellum / Q000187:drug effects / Q000201:enzymology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D009021:Morphine Dependence / Q000201:enzymology; D019331:NG-Nitroarginine Methyl Ester; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D009294:Narcotics / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013237:Stereoisomerism; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000201:enzymology*
D009292:Narcotic Antagonists; D009294:Narcotics; D009569:Nitric Oxide; D009270:Naloxone; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester