title: Neurobehavioral phenotype of C57BL/6J mice prenatally and neonatally exposed to cigarette smoke.
abstract: Although maternal cigarette smoking during pregnancy is a well-documented risk factor for a variety of adverse pregnancy outcomes, how prenatal cigarette smoke exposure affects postnatal neurobehavioral/cognitive development remains poorly defined. In order to investigate the cause of an altered behavioral phenotype, mice developmentally exposed to a paradigm of 'active' maternal cigarette smoke is needed. Accordingly, cigarette smoke exposed (CSE) and air-exposed C57BL/6J mice were treated for 6h per day in paired inhalation chambers throughout gestation and lactation and were tested for neurobehavioral effects while controlling for litter effects. CSE mice exhibited less than normal anxiety in the elevated zero maze, transient hypoactivity during a 1h locomotor activity test, had longer latencies on the last day of cued Morris water maze testing, impaired hidden platform learning in the Morris water maze during acquisition, reversal, and shift trials, and impaired retention for platform location on probe trials after reversal but not after acquisition or shift. CSE mice also showed a sexually dimorphic response in central zone locomotion to a methamphetamine challenge (males under-responded and females over-responded), and showed reduced anxiety in the light-dark test by spending more time on the light side. No differences on tests of marble burying, acoustic startle response with prepulse inhibition, Cincinnati water maze, matching-to-sample Morris water maze, conditioned fear, forced swim, or MK-801-induced locomotor activation were found. Collectively, the data indicate that developmental cigarette smoke exposure induces subnormal anxiety in a novel environment, impairs spatial learning and reference memory while sparing other behaviors (route-based learning, fear conditioning, and forced swim immobility). The findings add support to mounting evidence that developmental cigarette smoke exposure has long-term adverse effects on brain function.
authors: Department of Pediatrics, Division of Child Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, United States.
authors: Robyn M
authors: RM
authors: Amos-Kroohs
authors: Michael T
authors: MT
authors: Williams
authors: Amanda A
authors: AA
authors: Braun
authors: Devon L
authors: DL
authors: Graham
authors: Cynthia L
authors: CL
authors: Webb
authors: Todd S
authors: TS
authors: Birtles
authors: Robert M
authors: RM
authors: Greene
authors: Charles V
authors: CV
authors: Vorhees
authors: M Michele
authors: MM
authors: Pisano
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects; D003213:Conditioning, Psychological / Q000528:radiation effects; D002658:Developmental Disabilities / Q000139:chemically induced* / Q000503:physiopathology*; D005239:Fear / Q000187:drug effects / Q000523:psychology; D005260:Female; D007266:Inhibition, Psychological; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000503:physiopathology*; D012022:Reflex, Acoustic / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D062789:Tobacco Products / Q000633:toxicity*