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Major depression and dysthymia afflict a proportion of gravid and breast-feeding women. These women are frequently recommended on antidepressants to relieve their symptoms even if the drug effects on fetal growth and postnatal development are not completely known. In a previous study, we reported that prenatal bupropion exposure seemed to enhance the hedonic value of cocaine in adult mice. This study was undertaken to examine the dose-related effects for prenatal bupropion exposure on the stress susceptibility, cocaine-associated reinforcing property, and cocaine-induced behavioral sensitization in adult mice. Our results showed that various doses (ranging 12.5-50 mg/kg) of prenatal bupropion administration at the third trimester of pregnancy did not affect body weight of the adult mice. Bupropion administration at 50 mg/kg enhanced both ambulatory and rearing responses in the open field test. Moreover, bupropion administration (at 25 and 50 mg/kg) significantly decreased the numbers in open arm entry in the elevated plus maze test. Furthermore, prenatal bupropion treatment appeared to facilitate the cocaine-induced place preference in a sex-dependent manner. Finally, prenatal bupropion exposure (at 25 and 50 mg/kg) accelerated and elevated the development of cocaine-induced sensitization in locomotor activity. While the antidepressant and smoking-curbing effects of bupropion have been addressed in literature, we suggest that prenatal bupropion exposure could run a risk of enhancing individual's agitation, stress susceptibility and cocaine stimulating propensity in adulthood.