Abstract
Rationale
Only in Europe it can be estimated that more than 20 million of people would be affected by hypothyroidism in some moment of their life. Given that ethanol consumption is so frequent, it would be reasonable to ask what the consequences of ethanol consumption in those individuals affected by hypothyroidism are.
Objectives
To study the interaction between hypothyroidism and ethanol consumption.
Methods
We study ethanol consumption in a rat model of methyl-mercaptoimidazole-induced-adult-onset hypothyroidism and thyroid T4/T3 hormone supplementation. Also, we studied the effects of ethanol on motor activity, memory, and anxiety.
Results
We found that hypothyroidism increased the voluntary ethanol consumption and that this was enhanced by thyroid hormone supplementation. Hypothyroidism was associated with motor hyperactivity which was prevented either by T4/T3 supplementation or ethanol. The relationship between hypothyroidism, ethanol, and anxiety was more complex. In an anxiogenic context, hypothyroidism and T4/T3 supplementation would increase immobility, an anxiety-like behavior, while in a less anxiogenic context would decrease rearing, a behavior related to anxiety. Regarding memory, acute ethanol administration did not alter episodic-like memory in hypothyroid rats. Gene expression of enzymes involved in the metabolism of ethanol, i.e., Adh1 and Aldh2, were altered by hypothyroidism and T4/T3 supplementation.
Conclusions
Our results suggest that hypothyroid patients would need personalized attention in terms of ethanol consumption. In addition, they point that it would be useful to embrace the thyroid axis in the study of ethanol addiction, including as a possible therapeutic target for the treatment of alcoholism and its comorbid disorders.
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Abbreviations
- MMI:
-
Methyl-mercaptoimidazole
- T4:
-
L-thyroxine
- T3:
-
3,5,3′-Triiodothyronine
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Funding
This work was supported by the European Foundation for Alcohol Research (Ref. 12 21 to J.A.L.M., F.R.D.F., and R.M.), the Fondo de Investigación Sanitaria (Red de Trastornos Adictivos, FEDER, RD16/0017/0008 to J.A.L.M., RD12/0028/001 to F.R. D.F., and RD12/0028/023 to R.M.).
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All research was conducted in strict adherence to the European Directive 2010/63/EU and Royal Decree 53/2013 on the protection of animals used for scientific purposes. Animal studies are reported in compliance with the ARRIVE guidelines (Kilkenny et al. 2010). The Ethics Committee of the Faculty of Psychology of the Complutense University of Madrid approved the study.
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Fig. S1
Gene expression in the rat liver and prefrontal cortex. The effects of hypothyroidism, T4/T3 hormones and ethanol administration on mRNA levels of the main genes of the thyroid system (Trha, Trhb, Dio2, Dio3 and Tshr) and main enzymes involved in the metabolism of ethanol (Adh1 and Aldh2) in the rat liver and prefrontal cortex. Data represent the mean ± SEM (n = 9–12 per group) of the relative fold change obtained using the 2ΔCt method. *p < 0.05, **p < 0.01, ***p < 0.001 compared with its respective control group. # p < 0.05 compared with the water-control group. (JPG 1002 kb)
Table S1
Details of the primers used for quantitative real-time PCR of each gene. (RTF 138 kb)
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Echeverry-Alzate, V., Bühler, K.M., Calleja-Conde, J. et al. Adult-onset hypothyroidism increases ethanol consumption. Psychopharmacology 236, 1187–1197 (2019). https://doi.org/10.1007/s00213-018-5123-1
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DOI: https://doi.org/10.1007/s00213-018-5123-1