Effects of Maternal Separation on Nicotine-Induced Conditioned Place Preference and Later Spatial Learning and Memory Function in Adolescent Male Rats

Background: Disturbances in maternal care have been associated with increased risk for drug abuse later in life. However, there has been little investigation of the effects of maternal separation (MS), a model of early life stress, on nicotine dependence, specifically during adolescence. In the present study, we aimed to investigate the effect of MS on nicotine-conditioned place preference (CPP) in adolescent male rats. We also examined the impact of nicotine on spatial learning and memory impairments induced by MS.Methods: Rat pups were exposed to daily MS for 15 (MS15) or 180 (MS180) minutes during the first 2 weeks of life or reared under normal animal facility rearing (AFR) conditions. In postnatal day (PND) 28-34, they were conditioned with nicotine [0.6 mg/kg, subcutaneously (SC)] or saline and tested for preference over a period of 6 conditioning trials. Morris water maze (MWM) testing was performed to assess spatial cognitive function.Findings: The MS procedure used in our study failed to affect nicotine reward as measured by CPP in the adolescent male rats. Notably, significant spatial learning deficit was seen in the MS180 rats compared to those in the AFR and MS15 groups and nicotine administration modified the MS-induced learning defect in adolescent male rats.Conclusion: In conclusion, although MS revealed no influence on the sensitivity to the nicotine's reinforcing effects in adolescent male rats, the simultaneous effect of MS on learning performance may be altered by nicotine intake.