title: Sex and Adolescent Ethanol Exposure Influence Pavlovian Conditioned Approach.
abstract: Alcohol use among adolescents is widespread and a growing concern due to long-term behavioral deficits, including altered Pavlovian behavior, that potentially contribute to addiction vulnerability. We tested the hypothesis that adolescent intermittent ethanol (AIE) exposure alters Pavlovian behavior in males and females as measured by a shift from goal-tracking to sign-tracking. Additionally, we investigated GLT-1, an astrocytic glutamate transporter, as a potential contributor to a sign-tracking phenotype.
  
  
  
  Male and female Sprague-Dawley rats were exposed to AIE (5 g/kg, intragastric) or water intermittently 2 days on and 2 days off from postnatal day (P) 25 to 54. Around P70, animals began 20 daily sessions of Pavlovian conditioned approach (PCA), where they learned that a cue predicted noncontingent reward delivery. Lever pressing indicated interaction with the cue, or sign-tracking, and receptacle entries indicated approach to the reward delivery location, or goal-tracking. To test for effects of AIE on nucleus accumbens (NAcc) excitatory signaling, we isolated membrane subfractions and measured protein levels of the glutamate transporter GLT-1 after animals completed behavior as a measure of glutamate homeostasis.
  
  
  
  Females exhibited elevated sign-tracking compared to males with significantly more lever presses, faster latency to first lever press, and greater probability to lever press in a trial. AIE significantly increased lever pressing while blunting goal-tracking, as indicated by fewer cue-evoked receptacle entries, slower latency to receptacle entry, and lower probability to enter the receptacle in a trial. No significant sex-by-exposure interactions were observed in sign- or goal-tracking metrics. Moreover, we found no significant effects of sex or exposure on membrane GLT-1 expression in the NAcc.
  
  
  
  Females exhibited enhanced sign-tracking compared to males, while AIE decreased goal-tracking compared to control exposure. Our findings support the hypothesis that adolescent binge ethanol can shift conditioned behavior from goal- to cue-directed in PCA, especially in females.
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, North Carolina.|Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Aric C
authors.identifier: 0000-0002-3715-8499
authors.initials: AC
authors.lastname: Madayag
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, North Carolina.|Neurobiology Curriculum, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Sierra J
authors.initials: SJ
authors.lastname: Stringfield
authors.affiliation: Neurobiology Curriculum, University of North Carolina, Chapel Hill, North Carolina.|Department of Psychology and Neuroscience, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Reissner
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, North Carolina.|Neurobiology Curriculum, University of North Carolina, Chapel Hill, North Carolina.|Department of Psychology and Neuroscience, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Boettiger
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, North Carolina.|Neurobiology Curriculum, University of North Carolina, Chapel Hill, North Carolina.|Department of Psychiatry, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Donita L
authors.identifier: 0000-0001-7540-3363
authors.initials: DL
authors.lastname: Robinson
mesh_terms: D000367:Age Factors; D000818:Animals; D063425:Binge Drinking / Q000523:psychology*; D003214:Conditioning, Classical / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects* / Q000502:physiology; D012737:Sex Factors
chemical_list: D000431:Ethanol
keywords: Binge; Conditioned Pavlovian Approach; Goal Tracker; Sign Tracker; Western Blot