A prenatal nicotine exposure mouse model of methylphenidate responsive ADHD-associated cognitive phenotypes.
Prenatal exposure to nicotine via cigarette smoke or other forms of tobacco use is a significant environmental risk factor for attention deficit hyperactivity disorder (ADHD). The neurobiological mechanisms underlying the link between prenatal nicotine exposure (PNE) and ADHD are not well understood. Animal models, especially rodent models, are beginning to bridge this gap in knowledge. Although ADHD is characterized by hyperactivity, inattention, impulsivity and working memory deficits, the majority of the animal models are based on only one or two ADHD associated phenotypes, in particular, hyperactivity or inattention. We report a PNE mouse model that displays the full range of ADHD associated behavioral phenotypes including working memory deficit, attention deficit and impulsive-like behavior. All of the ADHD-associated phenotypes respond to a single administration of a therapeutic equivalent dose of methylphenidate. In an earlier study, we showed that PNE produces hyperactivity, frontal cortical hypodopaminergic state and thinning of the cingulate cortex. Collectively, these data suggest that the PNE mouse model recapitulates key features of ADHD and may be a suitable preclinical model for ADHD research.
Center for Brain Repair and The Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, United States.
Jinmin
J
Zhu
Center for Brain Repair and The Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, United States.
Fangfang
F
Fan
Center for Brain Repair and The Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, United States.
Deirdre M
DM
McCarthy
Center for Brain Repair and The Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, United States.
Lin
L
Zhang
Center for Brain Repair and The Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, United States.
Elisa N
EN
Cannon
Pediatric Psychopharmacology, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States.
Thomas J
TJ
Spencer
Pediatric Psychopharmacology, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States.
Joseph
J
Biederman
Center for Brain Repair and The Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, United States. Electronic address: pradeep.bhide@med.fsu.edu.
Pradeep G
PG
Bhide
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications* / Q000209:etiology; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology*; D004326:Drinking / Q000187:drug effects; D004924:Escape Reaction / Q000187:drug effects; D005260:Female; D008098:Litter Size / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008774:Methylphenidate / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000633:toxicity; D018722:Nicotinic Agonists / Q000633:toxicity; D011247:Pregnancy / Q000187:drug effects; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000503:physiopathology*; D021641:Recognition, Psychology / Q000187:drug effects; D012737:Sex Factors
D000697:Central Nervous System Stimulants; D018722:Nicotinic Agonists; D008774:Methylphenidate; D009538:Nicotine
ADHD; Attention; Impulsivity; Methylphenidate; Prenatal nicotine; Working memory