Changes in motor and learning behaviors of rats prenatally exposed to WIN 55212-2, a cannabinoid receptor agonist

Introduction: Cannabis consumption during pregnancy may affect fetal growth, motor performance, memory and cognitive functions. Methods: Primiparous pregnant Wistar rats were randomly assigned to 4 treatment groups (6 rats per group) consisting of control and sham groups as well as 2 groups treated with Win. Win treated groups received daily s.c. injections of 0.5 or 1 mg/kg WIN suspended in 1% Tween 80 saline in a volume of 1 ml/kg from days 5 to 20 of pregnancy. Sham treated rats were given daily injections of 1% Tween 80 saline on the same days of pregnancy. Body weight, mortality, memory function and motor performance were assessed in the infants on the third, fifth and seventh weeks after birth. Righting responses in rat pups were also compared on the second day after birth. Results: Offsprings from Win (1mg/kg) treated rats exhibited a significant loss in the righting reflex on the 2nd day after birth, when compared to other groups. However, there was no statistically significant difference between groups regarding motor coordination assessed by rotarod test on the 3rd and 5th weeks after birth. Passive avoidance learning (PAL) test on 50-day-old rats showed that during the acquisition trials, approach latencies were not significantly different among all groups. However, in retention trials, which were performed 24 h and 7 days later, the avoidance latencies of rats exposed to 0.5 mg/Kg Win were significantly shorter than those of the control and sham animals. Win consumption during pregnancy did not induce significant changes in the body weight of pregnant rats on the first day and three weeks after pregnancy. Litter size (number of pups per delivery) was significantly reduced in 1 mg/kg Wintreated compared to 0.5 mg/kg Win-treated, sham treated and control groups (p<0. 001). The length of pregnancy in 1 mg/kg Win-exposed rats was also significantly shorter compared to control (p<0.001), 0.5 mg/kg win-treated (p<0.01), and sham (p<0.0001) rats. Conclusion: These findings suggest that prenatal exposure to Win, a cannabinoid agonist, probably induces a longterm alteration of the endocannabinoid system, which in turn affects learning and motor coordination ability.