title: Prenatal exposure to nicotine impairs performance of the 5-choice serial reaction time task in adult rats.
abstract: Cigarette smoking is associated with a wide variety of adverse reproductive outcomes, including increased infant mortality and decreased birth weight. Prenatal exposure to tobacco smoke, of which nicotine is a major teratogenic component, has also been linked to the acceleration of the risk for different psychiatric disorders, including conduct disorder and attention deficit hyperactivity disorder (ADHD). Whether this increased risk is influenced by the direct effects of gestational nicotine exposure on the developing fetus remains uncertain. In this study we provide experimental evidence for the effects of prenatal nicotine exposure on measures of attention and impulsivity in adult male rats. Offspring of females exposed during pregnancy to 0.06 mg/ml nicotine solution as the only source of water (daily consumption: 69.6±1.4 ml/kg; nicotine blood level: 96.0±31.9 ng/ml) had lower birth weight and delayed sensorimotor development measured by negative geotaxis, righting reflex, and grip strength. In the 5-choice serial reaction time test, adult rats showed increased numbers of anticipatory responses and omissions errors, more variable response times, and lower accuracy with evidence of delayed learning of the task demands when the 1 s stimulus duration was introduced. In contrast, prenatal nicotine exposure had no effect on exploratory locomotion or delay-discounting test. Prenatal nicotine exposure increased expression of the D5 dopamine receptor gene in the striatum, but did not change expression of other dopamine-related genes (DRD4, DAT1, NR4A2, and TH) in either the striatum or the prefrontal cortex. These data suggest a direct effect of prenatal nicotine exposure on important aspects of attention, inhibitory control, or learning later in life.
authors.affiliation: Institute of Psychiatry, King's College London, London, UK. tomasz.schneider@psy.ox.ac.uk
authors.forename: Tomasz
authors.initials: T
authors.lastname: Schneider
authors.forename: Nicholas
authors.initials: N
authors.lastname: Ilott
authors.forename: Giovana
authors.initials: G
authors.lastname: Brolese
authors.forename: Lisiane
authors.initials: L
authors.lastname: Bizarro
authors.forename: Philip J E
authors.initials: PJ
authors.lastname: Asherson
authors.forename: Ian P
authors.initials: IP
authors.lastname: Stolerman
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D002755:Choice Behavior / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced / Q000503:physiopathology*; D002658:Developmental Disabilities / Q000209:etiology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009483:Neuropsychological Tests; D009538:Nicotine / Q000009:adverse effects* / Q000097:blood; D018722:Nicotinic Agonists / Q000009:adverse effects*; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D011930:Reaction Time / Q000187:drug effects*; D050638:Receptors, Dopamine D4 / Q000235:genetics / Q000378:metabolism; D050641:Receptors, Dopamine D5 / Q000235:genetics / Q000378:metabolism; D012018:Reflex / Q000187:drug effects
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C493601:Drd4 protein, rat; C493607:Drd5 protein, rat; D018722:Nicotinic Agonists; C539884:Nr4a2 protein, rat; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; C493216:Slc6a3 protein, rat; D050638:Receptors, Dopamine D4; D050641:Receptors, Dopamine D5; D009538:Nicotine