Influence of idazoxan on analgesia, tolerance, and physical dependence of morphine in mice and rats in vivo.
OBJECTIVE
To study the influence of idazoxan (Ida), an antagonist of imidazoline receptors (I-R), on analgesia, tolerance, and physical dependence of morphine.


METHODS
The effects of Ida on pain threshold and morphine analgesia were observed in mouse acetic acid writhing test and 55 degrees C hot plate test. The effect of Ida on morphine tolerance and physical dependence were observed in mouse tolerant model and in mice and rat models.


RESULTS
Ida (3-9 mg/kg) significantly decreased the pain threshold by 120% in acetic acid writhing test and by 39% in 55 degrees C hot plate test of mice, respectively. It inhibited the analgesic effect of morphine in a dose-dependent manner. Ida promoted the development of tolerance to morphine in mice and induced the abstinence syndrome in morphine-dependent mice and rats similar to naloxone.


CONCLUSIONS
I-R and its endogenous ligand agmatine might participate in the pain threshold and influence morphine analgesia as well as negatively regulate tolerance to and physical dependence on morphine.
Su
R B
RB
Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China. QinBY@nic.bmi.ac.cn
Li
J
J
Gao
K
K
Pei
G
G
Qin
B Y
BY
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000698:Analgesia; D000818:Animals; D004361:Drug Tolerance; D005260:Female; D019329:Idazoxan / Q000494:pharmacology*; D007093:Imidazoles; D054755:Imidazoline Receptors; D008297:Male; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors*; D009021:Morphine Dependence / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000037:antagonists & inhibitors
D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D054755:Imidazoline Receptors; D011955:Receptors, Drug; D009020:Morphine; D019329:Idazoxan