Tocolytic effect of delta9-tetrahydrocannabinol in mice model of lipopolysaccharide--induced preterm delivery: role of nitric oxide.
BACKGROUND
In this study, we explained that exogenous cannabinoid, Delta(9)-tetrahydrocannabinol (THC), has a preventive effect in a murine model of lipopolysaccharide (LPS)-induced preterm delivery and the contribution of nitric oxide (NO) pathway as a mechanism involved in this process.


METHODS
Preterm delivery was induced by double dose of 35 microg/kg LPS with 3-hour interval on gestational day (gd) 15. Delta(9)-tetrahydrocannabinol was administered with (a) double dose (0.02, 0.05, 0.1, 0.5, 1, and 5 mg/kg) 1 hour before each LPS injection, on gd 15 and (b) single administration (0.05, 0.1, and 0.5 mg/kg,) on gds 13 and 14, and the double administration, 1 hour before each LPS injection. To assess the involved mechanism, either AM281 (CB1 receptor antagonist, 2 mg/kg) and AM630 (CB2 receptor antagonist, 5 mg/kg) or N(omega)-nitro-L-arginine methyl ester (L-NAME, 2 mg/kg) was administered 1 hour before each THC injection on gds 13, 14, and 15. The main outcome measurement was the incidence of preterm delivery after injection of last LPS dose. Any interaction in the incidence and time of preterm delivery was ruled out by administration of AM281, AM630, or L-NAME alone.


RESULTS
Chronic THC treatment (0.5 mg/kg) significantly decreased the incidence of LPS-induced premature labor and increased the delivery time. Both AM281 and L-NAME reversed THC-induced attenuation of preterm delivery rate and pregnancy duration. Unlike AM281, AM630 did not influence the rate of preterm delivery in THC-treated mice.


CONCLUSIONS
Delta(9)-Tetrahydrocannabinol contributes to the regulation of gestational duration in LPS-induced preterm delivery probably by NO coupling through the CB1 receptor.
Basic Medical Sciences Research Center, Imam Khomeini Hospital, Tehran, Iran.
Alaleh
A
Asghari-Roodsari
Ali
A
Lesani
Mehrak
M
Javadi-Paydar
Leila
L
Tabatabaeefar
Seyed Mohammad
SM
Tavangar
Abbas
A
Norouzi
Ahmad Reza
AR
Dehpour
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives; D013759:Dronabinol / Q000008:administration & dosage*; D005260:Female; D008070:Lipopolysaccharides; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009569:Nitric Oxide / Q000502:physiology*; D011247:Pregnancy; D047928:Premature Birth / Q000517:prevention & control*; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors; D015149:Tocolytic Agents / Q000008:administration & dosage*
D008070:Lipopolysaccharides; D043884:Receptor, Cannabinoid, CB1; D015149:Tocolytic Agents; C026512:arginine methyl ester; D009569:Nitric Oxide; D013759:Dronabinol; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester