Destructive Effects of Prenatal WIN 55212-2 Exposure on Central Nervous System of Neonatal Rats

Document Type : Original Article(s)


1 Assistant Professor, Neuroscience Research Center, Kerman University of Medical Sciences, Kerman, Iran

2 Researcher, Neuroscience Research Center, Kerman University of Medical Sciences, Kerman, Iran

3 Professor, Neuroscience Research Center, Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran


Background: Cannabinoid, particularly hashish and WIN 55212-2 (WIN), consumption during embryonic period may affect fetal growth, and the development of motor functioning, memory and cognitive functions. Therefore, the present study aimed to evaluate the effects of WIN 55212-2 during embryonic period on behavioral responses, as well as tissue and memory changes among neonatal rats. Methods: WIN treated groups subcutaneously received daily doses of 0.5 or 1 mg/kg WIN suspended in 1% Tween-80-saline (1 mL/kg) from days 5 to 20 of pregnancy. The vehicle group received 1% Tween-80-saline from days 5 to 20 of pregnancy. Three, five and seven weeks after birth, the effects of maternal WIN consumption on infants' body weight, mortality, histological changes, motor functioning, and memory function were assessed. Findings: Prenatal WIN consumption was associated with atrophy of cerebellum cortex in granular and Purkinje cells layers. WIN treatment of pregnant rats produced a significant decrease in the rearing frequency of the offspring, but significantly increased the grooming frequency at 22, 36 and 50 days of age. During the acquisition trials, approach latencies were not significantly different between all groups of rats (50 days old). When the trial was repeated 24 hours and seven days later (retention trial), the avoidance latencies of the WIN-exposed group were significantly shorter than those of the control and vehicle animals. The mortality percent was increased significantly and litter size was decreased significantly in WIN (1 mg/kg) treated rats compared to the control, vehicle and WIN (0.5 mg/kg) treatment groups. Conclusion: These findings suggested that prenatal exposure to WIN probably induces long-term alterations in histological, motor functioning, and learning and memory parameters.   Keywords: Hashish, WIN 55212-2, Cerebellum, Prenatal exposure, Memory, Motor functioning