Comparative effects of NG-monomethyl-L-arginine and MK-801 on the abstinence syndrome in morphine-dependent mice.
The effects of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide (NO) synthase and MK-801, an NMDA receptor antagonist on abrupt and naltrexone-precipitated abstinence symptoms were determined in male Swiss-Webster mice rendered dependent on morphine by subcutaneous implantation of a pellet containing 75 mg of morphine base for 3 days. Mice which served as controls were implanted with placebo pellets. Six hours after pellet removal, mice were injected intraperitoneally with either the vehicle or MK-801 (0.03, 0.1 and 0.3 mg/kg). Thirty minutes later the animals were injected with naltrexone subcutaneously (50 micrograms/kg) and the intensity of abstinence symptoms were determined. Of the three doses of MK-801 used, only 0.1 mg/kg dose inhibited the jumping behavior precipitated by naltrexone in morphine-dependent mice. Whereas the lower dose (0.03 mg/kg) of MK-801 increased, the higher doses of MK-801 (0.1 and 0.3 mg/kg) displayed a decrease in the formation of fecal boli. Administration of MK-801 did not affect the body weight loss observed during abrupt withdrawal (induced by removal of the pellets) in morphine-dependent mice. MK-801 at 0.1 mg/kg dose further decreased the body temperature during abrupt withdrawal in morphine-dependent mice. Other two doses of MK-801 (0.03 and 0.3 mg/kg) did not modify the hypothermia observed during abrupt morphine withdrawal. On the other hand, L-NMMA (0.02 to 4.0 mg/kg) injected intraperitoneally 15 min prior to the naltrexone administration blocked the stereotyped jumping response in a dose-dependent manner. Higher doses of L-NMMA 2.0 and 4.0 mg/kg also decreased the number of fecal boli formation.(ABSTRACT TRUNCATED AT 250 WORDS)
Thorat
S N
SN
Department of Pharmaceutics and Pharmacodynamics (M/C 865), University of Illinois at Chicago 60612.
Barjavel
M J
MJ
Matwyshyn
G A
GA
Bhargava
H N
HN
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009021:Morphine Dependence / Q000503:physiopathology*; D009271:Naltrexone; D019001:Nitric Oxide Synthase; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D019323:omega-N-Methylarginine
D016194:Receptors, N-Methyl-D-Aspartate; D019323:omega-N-Methylarginine; D009271:Naltrexone; D016291:Dizocilpine Maleate; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases