Correlation between inhibitions of morphine withdrawal and nitric-oxide synthase by agmatine.
OBJECTIVE
To study correlation between inhibitions of naloxone-precipitated withdrawal jumps and nitric-oxide synthase (NOS) activity by agmatine.


METHODS
NOS activities in mouse brain were measured by determination of concentration of [3H]citrulline, the product of [3H]arginine.


RESULTS
Agmatine inhibited NOS activity in naive and morphine-dependent mouse cerebellum, forebrain, and thalamus in substrate-competitive manner in vitro. Naloxone induced withdrawal jumps and an increase in NOS activity in cerebellum, forebrain, and thalamus of abstinent mice. Pretreatment of mice with morphine plus agmatine inhibited the effect of naloxone to precipitate withdrawal jumps and increase in NOS activity. The effect of agmatine was blocked by idazoxan.


CONCLUSIONS
The inhibitory effect of agmatine on naloxone-precipitated withdrawal jumps is related to its inhibition of NOS activity by substrate competitive manner and activation of imidazoline receptors.
Li
J
J
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China. Gongzh@nic.Emi.ac.cn
Li
X
X
Pei
G
G
Qin
B Y
BY
D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D008297:Male; D051379:Mice; D009021:Morphine Dependence / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D013375:Substance Withdrawal Syndrome / Q000201:enzymology*
D000376:Agmatine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse