Late emerging effects of prenatal and early postnatal nicotine exposure on the cholinergic system and anxiety-like behavior

• Published in: Neurotoxicology and teratology Vol. 32; no. 3; pp. 336 - 345
• Main Authors: Eppolito, Amy K, Bachus, Susan E, McDonald, Craig G, Meador-Woodruff, James H, Smith, Robert F
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-05-2010; Elsevier
• Subjects: Acetylcholine; Acetylcholinesterase - biosynthesis; Animals; Animals, Newborn; Anxiety - chemically induced; Anxiety - metabolism; Anxiety - psychology; Behavior, Animal - drug effects; Biological and medical sciences; Brain - drug effects; Brain - embryology; Brain - growth & development; Brain - metabolism; Elevated plus maze; Emergency; Extinction learning; Female; In situ hybridization; Male; Maze Learning - drug effects; Medical Education; Medical sciences; Nicotine - toxicity; Pregnancy; Prenatal Exposure Delayed Effects - chemically induced; Prenatal Exposure Delayed Effects - metabolism; Prenatal Exposure Delayed Effects - psychology; Rat; Rats; Rats, Long-Evans; Tobacco, tobacco smoking; Toxicology; Extinction learning; Acetylcholine; Rat; In situ hybridization; Elevated plus maze; Affect affectivity; Late; Rodentia; Exposure; Learning; Prenatal; Alkaloid; Vertebrata; Mammalia; Acquisition process; Postnatal; Animal; Neurotransmitter; Early; Anxiety; Behavior; Nicotine
• ISSN: 0892-0362; 1872-9738
• DOI: 10.1016/j.ntt.2009.12.009

Abstract Animal models of prenatal nicotine exposure clearly indicate that nicotine is a neuroteratogen. Some of the persisting effects of prenatal nicotine exposure include low birth weight, behavioral changes and deficits in cognitive function, although few studies have looked for neurobehavioral and neurochemical effects that might persist throughout the lifespan. Pregnant rats were given continuous infusions of nicotine (0.96 mg/kg/day or 2.0 mg/kg/day, freebase) continuing through the third trimester equivalent, a period of rapid brain development. Because the third trimester equivalent occurs postnatally in the rat (roughly the first week of life) nicotine administration to neonate pups continued via maternal milk until postnatal day (P) 10. Exposure to nicotine during pre- and early postnatal development had an anxiogenic effect on adult rats (P75) in the elevated plus maze (EPM), and blocked extinction learning in a fear conditioning paradigm, suggesting that pre- and postnatal nicotine exposure affect anxiety-like behavior and cognitive function well into adulthood. In contrast, nicotine exposure had no effect on anxiety-like behaviors in the EPM in adolescent animals (P30). Analysis of mRNA for the α4, α7, and β2 subunits of nicotinic acetylcholine receptors revealed lower expression of these subunits in the adult hippocampus and medial prefrontal cortex following pre- and postnatal nicotine exposure, suggesting that nicotine altered the developmental trajectory of the brain. These long-term behavioral and neurochemical changes strengthen the case for discouraging cigarette smoking during pregnancy and clearly indicate that the use of the patch as a smoking cessation aid during pregnancy is not a safe alternative.