title: Ifenprodil infusion in agranular insular cortex alters social behavior and vocalizations in rats exposed to moderate levels of ethanol during prenatal development.
abstract: Moderate exposure to alcohol during development leads to subtle neurobiological and behavioral effects classified under the umbrella term fetal alcohol spectrum disorders (FASDs). Alterations in social behaviors are a frequently observed consequence of maternal drinking, as children with FASDs display inappropriate aggressive behaviors and altered responses to social cues. Rodent models of FASDs mimic the behavioral alterations seen in humans, with rats exposed to ethanol during development displaying increased aggressive behaviors, decreased social investigation, and altered play behavior. Work from our laboratory has observed increased wrestling behavior in adult male rats following prenatal alcohol exposure (PAE), and increased expression of GluN2B-containing NMDA receptors in the agranular insular cortex (AIC). This study was undertaken to determine if ifenprodil, a GluN2B preferring negative allosteric modulator, has a significant effect on social behaviors in PAE rats. Using a voluntary ethanol exposure paradigm, rat dams were allowed to drink a saccharin-sweetened solution of either 0% or 5% ethanol throughout gestation. Offspring at 6-8 months of age were implanted with cannulae into AIC. Animals were isolated for 24h before ifenprodil or vehicle was infused into AIC, and after 15min they were recorded in a social interaction chamber. Ifenprodil treatment altered aspects of wrestling, social investigatory behaviors, and ultrasonic vocalizations in rats exposed to ethanol during development that were not observed in control animals. These data indicate that GluN2B-containing NMDA receptors in AIC play a role in social behaviors and may underlie alterations in behavior and vocalizations observed in PAE animals.
authors.affiliation: Department of Psychology, University of New Mexico, Albuquerque, NM, United States; Department of Neurosciences, University of New Mexico, Albuquerque, NM, United States. Electronic address: cbird@salud.unm.edu.
authors.forename: Clark W
authors.initials: CW
authors.lastname: Bird
authors.affiliation: Department of Psychology, University of New Mexico, Albuquerque, NM, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Barto
authors.affiliation: Department of Psychology, University of New Mexico, Albuquerque, NM, United States.
authors.forename: Christy M
authors.initials: CM
authors.lastname: Magcalas
authors.affiliation: Department of Psychology, University of New Mexico, Albuquerque, NM, United States.
authors.forename: Carlos I
authors.initials: CI
authors.lastname: Rodriguez
authors.affiliation: Department of Psychology, University of New Mexico, Albuquerque, NM, United States.
authors.forename: Tia
authors.initials: T
authors.lastname: Donaldson
authors.affiliation: Department of Neurosciences, University of New Mexico, Albuquerque, NM, United States.
authors.forename: Suzy
authors.initials: S
authors.lastname: Davies
authors.affiliation: Department of Psychology, University of New Mexico, Albuquerque, NM, United States; Department of Neurosciences, University of New Mexico, Albuquerque, NM, United States.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Savage
authors.affiliation: Department of Psychology, University of New Mexico, Albuquerque, NM, United States; Department of Neurosciences, University of New Mexico, Albuquerque, NM, United States.
authors.forename: Derek A
authors.initials: DA
authors.lastname: Hamilton
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002492:Central Nervous System Depressants / Q000097:blood / Q000633:toxicity; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000097:blood / Q000633:toxicity; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005260:Female; D008297:Male; D010880:Piperidines / Q000627:therapeutic use*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D020318:Rats, Long-Evans; D012737:Sex Factors; D012919:Social Behavior; D013997:Time Factors; D014828:Vocalization, Animal / Q000187:drug effects*
chemical_list: D002492:Central Nervous System Depressants; D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D000431:Ethanol; C010739:ifenprodil
keywords: Agranular insular cortex; GluN2B; Ifenprodil; Social behavior; Ultrasonic vocalizations