Prenatal cigarette smoke exposure causes hyperactivity and aggressive behavior: role of altered catecholamines and BDNF.
Smoking during pregnancy is associated with a variety of untoward effects on the offspring. However, recent epidemiological studies have brought into question whether the association between neurobehavioral deficits and maternal smoking is causal. We utilized an animal model of maternal smoking to determine the effects of prenatal cigarette smoke (CS) exposure on neurobehavioral development. Pregnant mice were exposed to either filtered air or mainstream CS from gestation day (GD) 4 to parturition for 4h/d and 5d/wk, with each exposure producing maternal plasma concentration of cotinine equivalent to smoking <1 pack of cigarettes per day (25ng/ml plasma cotinine level). Pups were weaned at postnatal day (PND) 21 and behavior was assessed at 4weeks of age and again at 4-6months of age. Male, but not female, offspring of CS-exposed dams demonstrated a significant increase in locomotor activity during adolescence and adulthood that was ameliorated by methylphenidate treatment. Additionally, male offspring exhibited increased aggression, as evidenced by decreased latency to attack and number of attacks in a resident-intruder task. These behavioral abnormalities were accompanied by a significant decrease in striatal and cortical dopamine and serotonin and a significant reduction in brain-derived neurotrophic factor (BDNF) mRNA and protein. Taken in concert, these data demonstrate that prenatal exposure to CS produces behavioral alterations in mice that are similar to those observed in epidemiological studies linking maternal smoking to neurodevelopmental disorders. Further, these data also suggest a role for monaminergic and BDNF alterations in these effects.
Environmental and Occupational Health Sciences Institute, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Department of Environmental and Occupational Medicine, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
Carrie
C
Yochum
Department of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA.
Shannon
S
Doherty-Lyon
Department of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA.
Carol
C
Hoffman
Environmental and Occupational Health Sciences Institute, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Department of Environmental and Occupational Medicine, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
Muhammad M
MM
Hossain
Department of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA. Electronic address: Judith.zelikoff@nyumc.org.
Judith T
JT
Zelikoff
Environmental and Occupational Health Sciences Institute, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Department of Environmental and Occupational Medicine, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA. Electronic address: Jricha3@eohsi.rutgers.edu.
Jason R
JR
Richardson
D000374:Aggression / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006948:Hyperkinesis / Q000209:etiology* / Q000378:metabolism; D008098:Litter Size; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology* / Q000378:metabolism; D012727:Sex Characteristics; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D019208:Brain-Derived Neurotrophic Factor; D002395:Catecholamines; D014028:Tobacco Smoke Pollution
ADHD; Aggression; BDNF; Dopamine; Hyperactivity; Maternal smoking; Nicotine