Neonatal alcohol and nicotine exposure limits brain growth and depletes cerebellar Purkinje cells

Abstract

The present study examined the effects of coexposure of alcohol and nicotine during the brain growth spurt period on brain weights and cerebellar Purkinje cell numbers. Sprague-Dawley rat pups were randomly assigned into five groups (four artificially reared groups and one suckle control). Artificially reared pups were given alcohol (0 or 4 g/kg/day) and/or nicotine (0 or 6 mg/kg/day) daily from postnatal days (PDs) 4 to 9, and the suckle controls received no experimental treatments. The results are summarized below. (1) Surprisingly, nicotine reduced the peak blood alcohol concentration from about 300 to 230 mg/dl, but alcohol did not affect urine cotinine levels (approximately 12,000-13,000 ng/ml). (2) Alcohol significantly reduced the weights of forebrain, cerebellum, and brain stem, but nicotine limited only the growth of the forebrain. (3) Purkinje cell numbers in the cerebellar vermis were significantly reduced in response to alcohol, nicotine, and the combination of both drugs. (4) No statistically significant interactive effect was found following the cotreatment of alcohol and nicotine. Collectively, the present study replicated our previous findings demonstrating alcohol's detrimental effects on brain development; it also presented new evidence documenting nicotine's neuroteratogenic effects on restricting brain growth and depleting cerebellar Purkinje cells during the brain growth spurt.