Sex-dependent effects of chronic intermittent ethanol treatment in Wistar rats

Authors

  • Mariia Dorofeikova Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, pr. Toreza, 44, Saint Petersburg, 194223, Russian Federation; Center for Molecular Neurobiology Hamburg, Falkenried, 94, Hamburg, 20251, Germany https://orcid.org/0000-0002-2181-2281
  • Irina Antonova Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, pr. Toreza, 44, Saint Petersburg, 194223, Russian Federation
  • Galina Gromova Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, pr. Toreza, 44, Saint Petersburg, 194223, Russian Federation
  • Anastasia Veraksa Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, pr. Toreza, 44, Saint Petersburg, 194223, Russian Federation
  • Elena Filatova Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, pr. Toreza, 44, Saint Petersburg, 194223, Russian Federation https://orcid.org/0000-0003-1321-1053
  • Alexei Egorov Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, pr. Toreza, 44, Saint Petersburg, 194223, Russian Federation https://orcid.org/0000-0002-5737-8560

DOI:

https://doi.org/10.21638/spbu03.2023.304

Abstract

Multiple behavioral parameters are associated with vulnerability to alcohol dependence, but the contribution of such factors as cognitive flexibility and sex differences still require further clarification. Our goal was to assess how sex differences mediate relationships between cognitive flexibility, affective state, hierarchy and ethanol preference before and after chronic intermittent ethanol (CIE) exposure in Wistar rats. The results of our study revealed sex-dependent changes in ethanol preference and locomotor activity throughout the time. Anxiety levels were sex-dependently affected by ethanol exposure with a dramatic decrease in ethanol-exposed females. Similarly, striatal tyrosine hydroxylase expression was affected by CIE in a sex-dependent manner, with ethanol-exposed females having higher expression than males. Baseline cognitive flexibility was better in rats with higher locomotor activity and lower anxiety levels but did not correlate with ethanol preference in rats. Taken together, these results are important for understanding sex-dependent alterations in brain and behavior induced by alcohol. This provides important insights into understanding sex differences in the risk for mental disorders.

Keywords:

chronic intermittent ethanol exposure, ethanol preference, alcohol, sex differences, anxiety, cognitive flexibility, tyrosine hydroxylase, striatum, rat

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References

Aguirre, C. G., Stolyarova, A., Das, K., Kolli, S., Marty, V., Ray, L., Spigelman, I., and Izquierdo, A. 2020. Sex-dependent effects of chronic intermittent voluntary alcohol consumption on attentional, not motivational, measures during probabilistic learning and reversal. PloS ONE 15(6):e0234729. https://doi.org/10.1371/journal.pone.0234729

Bach, E. C., Morgan, J. W., Ewin, S. E., Barth, S. H., Raab-Graham, K. F., and Weiner, J. L. 2021. Chronic ethanol exposures leads to a negative affective state in female rats that is accompanied by a paradoxical decrease in ventral hippocampus excitability. Frontiers in Neuroscience 15:669075. https://doi.org/10.3389/fnins.2021.669075

Becker, J. B. and Koob, G. F. 2016. Sex differences in animal models: focus on addiction. Pharmacological Reviews 68(2):242–263. https://doi.org/10.1124/pr.115.011163

Bickel, W. K., Jarmolowicz, D. P., Mueller, E. T., Gatchalian, K. M., and McClure, S. M. 2012. Are executive function and impulsivity antipodes? A conceptual reconstruction with special reference to addiction. Psychopharmacology 221(3):361–387. https://doi.org/10.1007/s00213-012-2689-x

Cao, J., Willett, J. A., Dorris, D. M., and Meitzen, J. 2018. Sex differences in medium spiny neuron excitability and glutamatergic synaptic input: heterogeneity across striatal regions and evidence for estradiol-dependent sexual differentiation. Frontiers in Endocrinology 9:173. https://doi.org/10.3389/fendo.2018.00173

Collins, S. E. 2016. Associations between socioeconomic factors and alcohol outcomes. Alcohol Research: Current Reviews 38(1):83–94.

Costa, D. F., Moita, M. A., and Márquez, C. 2021. Novel competition test for food rewards reveals stable dominance status in adult male rats. Scientific Reports 11(1):14599. https://doi.org/10.1038/s41598-021-93818-0

DiLeo, A., Antonoudiou, P., Ha, S., and Maguire, J. L. 2022. Sex differences in the alcohol-mediated modulation of BLA network states. eNeuro 9(4):ENEURO.0010-22.2022. https://doi.org/10.1523/ENEURO.0010-22.2022

Feltmann, K., Borroto-Escuela, D. O., Rüegg, J., Pinton, L., de Oliveira Sergio, T., Narváez, M., Jimenez-Beristain, A., Ekström, T. J., Fuxe, K., and Steensland, P. 2018. Effects of long-term alcohol drinking on the dopamine D2 receptor: gene expression and heteroreceptor complexes in the striatum in rats. Alcoholism, Clinical and Experimental Research 42(2):338–351. https://doi.org/10.1111/acer.13568

Filatova, E. V., Gromova, G. E., Dorofeikova, M. V., Antonova, I. V., and Egorov, A. Yu. 2022. Comparative study of the behavior of Wistar rats, dopamine transporter heterozygous rats and rats after long-term ethanol consumption in the Morris water maze. Journal of Evolutionary Biochemistry and Physiology 58:1653–1663. https://doi.org/10.1134/S0022093022050337

Flores-Bonilla, A. and Richardson, H. N. 2020. Sex differences in the neurobiology of alcohol use disorder. Alcohol Research: Current Reviews 40(2):04. https://doi.org/10.35946/arcr.v40.2.04

Giacometti, L. L. and Barker, J. M. 2020. Sex differences in the glutamate system: Implications for addiction. Neuroscience and Biobehavioral Reviews 113:157–168. https://doi.org/10.1016/j.neubiorev.2020.03.010

Glass, J. M., Buu, A., Adams, K. M., Nigg, J. T., Puttler, L. I., Jester, J. M., and Zucker, R. A. 2009. Effects of alcoholism severity and smoking on executive neurocognitive function. Addiction 104(1):38–48. https://doi.org/10.1111/j.1360-0443.2008.02415.x

Healey, K. L., Kibble, S. A., Bell, A., Kramer, G., Maldonado-Devincci, A., and Swartzwelder, H. S. 2022. Sex differences in the effects of adolescent intermittent ethanol exposure on exploratory and anxiety-like behavior in adult rats. Alcohol 98:43–50. https://doi.org/10.1016/j.alcohol.2021.11.002

Hitzemann, R., Bergeson, S. E., Berman, A. E., Bubier, J. A., Chesler, E. J., Finn, D. A., Hein, M., Hoffman, P., Holmes, A., Kisby, B. R., Lockwood, D., Lodowski, K. H., McManus, M., Owen, J. A., Ozburn, A. R., Panthagani, P., Ponomarev, I., Saba, L., Tabakoff, B., Walchale, A., Williams, R. W., and Phillips, T. J. 2022. Sex differences in the brain transcriptome related to alcohol effects and alcohol use disorder. Biological Psychiatry 91(1):43–52. https://doi.org/10.1016/j.biopsych.2021.04.016

Hu, W., Morris, B., Carrasco, A., and Kroener, S. 2015. Effects of acamprosate on attentional set-shifting and cellular function in the prefrontal cortex of chronic alcohol-exposed mice. Alcoholism, Clinical and Experimental Research 39(6):953–961. https://doi.org/10.1111/acer.12722

Hughes, R. N. 1990. Sex-dependent habituation to novelty in rats. Current Psychology 9:277–284. https://doi.org/10.1007/BF02686865

Ibáñez-Sandoval, O., Xenias, H. S., Tepper, J. M., and Koós, T. 2015. Dopaminergic and cholinergic modulation of striatal tyrosine hydroxylase interneurons. Neuropharmacology 95:468–476. https://doi.org/10.1016/j.neuropharm.2015.03.036

Jaafari Suha, A., Hosseinmardi, N., and Janahmadi, M. 2022. Spatial working memory is disparately interrelated with social status through different developmental stages in rats. Behavioural Brain Research 416:113547. https://doi.org/10.1016/j.bbr.2021.113547

Juárez, J. and Barrios de Tomasi, E. 1999. Sex differences in alcohol drinking patterns during forced and voluntary consumption in rats. Alcohol 19(1):15–22. https://doi.org/10.1016/s0741-8329(99)00010-5

Koob, G. F. and Volkow, N. D. 2010. Neurocircuitry of Addiction. Neuropsychopharmacology 35(1):217-238. https://doi.org/10.1038/npp.2009.110

Kristofiková, Z., Platilová, V., and Klaschka, J. 2003. Age- and sex-dependent effects of ethanol on hippocampal hemicholinium-3 sensitive choline carriers during postnatal development of rats. Neurochemical Research 28(3–4):397–405. https://doi.org/10.1023/a:1022832214475

Kroener, S., Mulholland, P. J., New, N. N., Gass, J. T., Becker, H. C., and Chandler, L. J. 2012. Chronic alcohol exposure alters behavioral and synaptic plasticity of the rodent prefrontal cortex. PLoS ONE 7(5):e37541. https://doi.org/10.1371/journal.pone.0037541

Levy, D. R., Hunter, N., Lin, S., Robinson, E. M., Gillis, W., Conlin, E. B., Anyoha, R., Shansky, R. M., and Datta, S. R. 2023. Mouse spontaneous behavior reflects individual variation rather than estrous state. Current Biology 33(7):1358–1364.e4. https://doi.org/10.1016/j.cub.2023.02.035

Logrip, M. L., Oleata, C., and Roberto, M. 2017. Sex differences in responses of the basolateral-central amygdala circuit to alcohol, corticosterone and their interaction. Neuropharmacology 114:123–134. https://doi.org/10.1016/j.neuropharm.2016.11.021

Lovick, T. A. and Zangrossi, H., Jr. 2021. Effect of estrous cycle on behavior of females in rodent tests of anxiety. Frontiers in Psychiatry 12:711065. https://doi.org/10.3389/fpsyt.2021.711065

Menezes, J., Souto das Neves, B. H., Gonçalves, R., Benetti, F., and Mello-Carpes, P. B. 2020. Maternal deprivation impairs memory and cognitive flexibility, effect that is avoided by environmental enrichment. Behavioural Brain Research 381:112468. https://doi.org/10.1016/j.bbr.2020.112468

Mineur, Y. S., Garcia-Rivas, V., Thomas, M. A., Soares, A. R., McKee, S. A., and Picciotto, M. R. 2022. Sex differences in stress-induced alcohol intake: a review of preclinical studies focused on amygdala and inflammatory pathways. Psychopharmacology 239(7):2041–2061. https://doi.org/10.1007/s00213-022-06120-w

Pleil, K. E., Lowery-Gionta, E. G., Crowley, N. A., Li, C., Marcinkiewcz, C. A., Rose, J. H., McCall, N. M., Maldonado-Devincci, A. M., Morrow, A. L., Jones, S. R., and Kash, T. L. 2015. Effects of chronic ethanol exposure on neuronal function in the prefrontal cortex and extended amygdala. Neuropharmacology 99:735–749. https://doi.org/10.1016/j.neuropharm.2015.06.017

Pleil, K. E. and Skelly, M. J. 2018. CRF modulation of central monoaminergic function: Implications for sex differences in alcohol drinking and anxiety. Alcohol 72:33–47. https://doi.org/10.1016/j.alcohol.2018.01.007

Risher, M. L., Fleming, R. L., Boutros, N., Semenova, S., Wilson, W. A., Levin, E. D., Markou, A., Swartzwelder, H. S., and Acheson, S. K. 2013. Long-term effects of chronic intermittent ethanol exposure in adolescent and adult rats: radial-arm maze performance and operant food reinforced responding. PloS ONE 8(5):e62940. https://doi.org/10.1371/journal.pone.0062940

Rodberg, E. M. and Vazey, E. M. 2022. Individual differences in behavioral flexibility predict future volitional ethanol consumption in mice. Alcohol 101:37–43. https://doi.org/10.1016/j.alcohol.2022.03.003

Scott, H., Tjernström, N., and Roman, E. 2020. Effects of pair housing on voluntary alcohol intake in male and female Wistar rats. Alcohol 86:121–128. https://doi.org/10.1016/j.alcohol.2019.12.005

Schneider, P., Ho, Y. J., Spanagel, R., and Pawlak, C. R. 2011. A novel elevated plus-maze procedure to avoid the onetrial tolerance problem. Frontiers in Behavioral Neuroscience 5:43. https://doi.org/10.3389/fnbeh.2011.00043

Schrader, A. J., Taylor, R. M., Lowery-Gionta, E. G., and Moore, N. L. T. 2018. Repeated elevated plus maze trials as a measure for tracking within-subjects behavioral performance in rats (Rattus norvegicus). PloS ONE 13(11):e0207804. https://doi.org/10.1371/journal.pone.0207804

Shnitko, T. A., Gonzales, S. W., and Grant, K. A. 2019. Low cognitive flexibility as a risk for heavy alcohol drinking in non-human primates. Alcohol 74:95–104. https://doi.org/10.1016/j.alcohol.2018.04.007

Sneddon, E. A., Ramsey, O. R., Thomas, A., and Radke, A. K. 2020. Increased responding for alcohol and resistance to aversion in female mice. Alcoholism, Clinical and Experimental Research 44(7):1400–1409. https://doi.org/10.1111/acer.14384

Troshev, D., Bannikova, A., Blokhin, V., Kolacheva, A., Pronina, T., and Ugrumov, M. 2022. Striatal neurons partially expressing a dopaminergic phenotype: functional significance and regulation. International Journal of Molecular Sciences 23:11054. https://doi.org/10.3390/ijms231911054

Walf, A. A. and Frye, C. A. 2007. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nature Protocols 2(2):322–328. https://doi.org/10.1038/nprot.2007.44

Xenias, H. S., Ibáñez-Sandoval, O., Koós, T., and Tepper, J. M. 2015. Are striatal tyrosine hydroxylase interneurons dopaminergic? Journal of Neuroscience 35(16):6584–6599. https://doi.org/10.1523/JNEUROSCI.0195-15.2015

Xie, Q., Buck, L. A., Bryant, K. G., and Barker, J. M. 2019. Sex differences in ethanol reward seeking under conflict in mice. Alcoholism, Clinical and Experimental Research 43(7):1556–1566. https://doi.org/10.1111/acer.14070

Zachry, J. E., Johnson, A. R., and Calipari, E. S. 2019. Sex differences in value-based decision making underlie substance use disorders in females. Alcohol and Alcoholism 54(4):339–341. https://doi.org/10.1093/alcalc/agz052

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Published

2023-11-30

How to Cite

Dorofeikova, M., Antonova, I., Gromova, G., Veraksa, A., Filatova, E., & Egorov, A. (2023). Sex-dependent effects of chronic intermittent ethanol treatment in Wistar rats. Biological Communications, 68(3), 164–172. https://doi.org/10.21638/spbu03.2023.304

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