Effects Of Cocaine Exposure On Behavior And Development Of Brain Neurons In Offspring During Pregnancy

Converging evidence from both human and animal studies indicates that prenatal cocaine exposure produces long lasting cognitive and affective neurobehavioral changes. Both in vitro and in vivo researches have shown that cocaine affects neural development including proliferation, apoptosis, differentiation, migration and dendrite morphology, thus produces enduring changes in the formation and function of brain circuits. The behavioral deficits may result from the effects on brain development by prenatal exposure to cocaine.This research applies some behavioral model distinguished from those used in previous studies to investigate the impacts of prenatal exposure to cocaine (cocaine, s.c.20mg/kg, twice a day, E8.5-E17.5) on behaviors of learning and memory, and social interaction of offspring in adult. Using in utero electroporation of EYFP plasmid to trace the developing neurons in the primary somatosensory cortex of mice, we investigate the effects of prenatal cocaine exposure on the migration and dendrite morphogenesis of the cortical layer Ⅱ/Ⅲ neurons in vivo at different developmental stage.The physical growth results show that:Prenatal exposure to cocaine didn’t affect the maternal or offspring mice outcome including maternal weight gain, gestation duration, litter size, offspring body weight at birth and at the adulthood.The behavioral results show that:1) Prenatal exposure to cocaine did not change the spontaneous motion ability, the exploration desire and emotion state of offspring adult mice in the open field test.2) Prenatal exposure to cocaine did not impaire the object recognition short term memory of offspring adult mice in object recognition task (ORT). The result also suggests that prenatal exposure to cocaine didn’t affect the object exploration level, the object discrimination ability and the novel object preference of mice.3) Prenatal cocaine exposured offspring showed impaired spatial memory in object location task. With an one-hour interval between training phase and test phase, prenatal cocaine exposured offspring mice did not show a preference to the object in novel location as the wide-type mice did. This result indicates that prenatal cocaine exposure leads to the deficiency in spatial related memory.4) The prenatal cocaine exposured offspring mice showed the same performance in social behavior test compared with the saline offspring, which indicates that prenatal cocaine exposure does not impair the sociability and social novelty preference in social interaction behaviors of mice.The morphologic results show that:1) Prenatal cocaine exposure has no significant effect on the migration and polarization of developing layer Ⅱ/Ⅲ neurons and the radial glial fibers morphology in the primary somatosensory cortex.2) Prenatal cocaine exposure induces abnormal dendrite morphogenesis of the layer Ⅱ/Ⅲ projection neurons at the primary somatosensory cortical region. By in utero electroporation labeling, the cortical neurons of prenatal cocaine exposure offspring at PO and P3demonstrated significant more dendritic branch number and longer length compared with saline offspring.In summary, our research first show that:1) Prenatal cocaine exposure impairs spacial memory of offspring mice in object location task, and this deficit does not result from object exploration level, object discrimination ability, novel object preference and the memory retention of object recognition.2) Prenatal cocaine exposure induces abnormal dendrite outgrowth and morphology of the layer Ⅱ/Ⅲ projection neurons in the primary somatosensory cortex of offspring mice, but has no significant effect on the migration of these neurons.