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Sex and Adolescent Ethanol Exposure Influence Pavlovian Conditioned Approach.
Alcohol Clin Exp Res 2017; 41(4):846-856AC

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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+Show Affiliations

Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, North Carolina. Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina.Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, North Carolina. Neurobiology Curriculum, 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.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.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.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

28196273

Citation

Madayag, Aric C., et al. "Sex and Adolescent Ethanol Exposure Influence Pavlovian Conditioned Approach." Alcoholism, Clinical and Experimental Research, vol. 41, no. 4, 2017, pp. 846-856.
Madayag AC, Stringfield SJ, Reissner KJ, et al. Sex and Adolescent Ethanol Exposure Influence Pavlovian Conditioned Approach. Alcohol Clin Exp Res. 2017;41(4):846-856.
Madayag, A. C., Stringfield, S. J., Reissner, K. J., Boettiger, C. A., & Robinson, D. L. (2017). Sex and Adolescent Ethanol Exposure Influence Pavlovian Conditioned Approach. Alcoholism, Clinical and Experimental Research, 41(4), pp. 846-856. doi:10.1111/acer.13354.
Madayag AC, et al. Sex and Adolescent Ethanol Exposure Influence Pavlovian Conditioned Approach. Alcohol Clin Exp Res. 2017;41(4):846-856. PubMed PMID: 28196273.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sex and Adolescent Ethanol Exposure Influence Pavlovian Conditioned Approach. AU - Madayag,Aric C, AU - Stringfield,Sierra J, AU - Reissner,Kathryn J, AU - Boettiger,Charlotte A, AU - Robinson,Donita L, Y1 - 2017/03/13/ PY - 2016/08/29/received PY - 2017/02/08/accepted PY - 2017/2/15/pubmed PY - 2017/12/19/medline PY - 2017/2/15/entrez KW - Binge KW - Conditioned Pavlovian Approach KW - Goal Tracker KW - Sign Tracker KW - Western Blot SP - 846 EP - 856 JF - Alcoholism, clinical and experimental research JO - Alcohol. Clin. Exp. Res. VL - 41 IS - 4 N2 - BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. SN - 1530-0277 UR - https://www.unboundmedicine.com/medline/citation/28196273/Sex_and_Adolescent_Ethanol_Exposure_Influence_Pavlovian_Conditioned_Approach L2 - https://doi.org/10.1111/acer.13354 DB - PRIME DP - Unbound Medicine ER -