Effects of low-dose alcohol exposure in adolescence on subsequent alcohol drinking in adulthood in a rat model of depression

Abstract

Objective

Adolescence drinking and subsequent development of alcohol use disorder (AUD) is a worldwide health concern. In particular, mood dysregulation or early alcohol exposure can be the cause of heavy drinking in some individuals or a consequence of heavy drinking in others.

Methods

This study investigated the effects of voluntary alcohol intake during adolescence, i.e. continuous 10% alcohol access between postnatal days (PND) 29 to 43 and olfactory bulbectomy (OBX) model of depression (performed on PND 59) on alcohol drinking in Wistar rats during adulthood (PND 80–120, intermittent 20% alcohol access). In addition, the effect of NBQX, an AMPA/kainate receptor antagonist (5 mg/kg, IP) on spontaneous alcohol consumption was examined.

Results

Rats exposed to 10% alcohol during adolescence exhibited a lower 20% alcohol intake in the intermittent paradigm during adulthood, while the OBX-induced phenotype did not exert a significant effect on the drinking behaviour. NBQX exerted a transient reduction on alcohol intake in the OBX rats.

Conclusions

Our results indicate that exposure to alcohol during adolescence can affect alcohol drinking in adulthood and that further exploration of AMPA and/or kainate receptor antagonists in co-morbid alcoholism-depression is warranted.

Keywords:

• Alcohol use disorder
• AMPA/kainate receptor
• depression
• NBQX
• olfactory bulbectomy
• rats

Acknowledgements

The authors are grateful to Petra Kamenikova and Marcela Kucirkova for their expert support in behavioural testing and excellent animal care. Our gratitude also belongs to Tony Fong from University of British Columbia (Vancouver, Canada) for proof-reading.

Statement of interest

None to declare.

Additional information

Funding

This study, in collaboration with investigators at Howard University in Washington, DC (supported by NIH/NIAAA R03AA022479, YT), was performed at Masaryk University as part of the project ‘Preclinical and clinical student research in the field of pharmacokinetics, neuropsychopharmacology and personalised pharmacotherapy in oncology’, number MUNI/A/1292/2019, and the project ‘Pharmacological research in the field of pharmacokinetics, neuropsychopharmacology and oncology’ number MUNI/A/1249/2020 with the support of the Specific University Research Grant, as provided by the Ministry of Education, Youth and Sports of the Czech Republic (MEYS CR) in the year 2020 and 2021, respectively, and by funds from the Faculty of Medicine MU to junior researcher Jana Ruda-Kucerova. DK was also supported by a specific research grant of Masaryk University (MUNI/A/1615/2020).