A Rat Model of the Brain-Derived Neurotrophic Factor Val66Met Polymorphism Shows Attenuated Motivation for Alcohol Self-Administration and Diminished Propensity for Cue-Induced Relapse in Females

Emily J. Jaehne; Elizabeth McInerney; Ronan Sharma; Shannyn G. Genders; Elvan Djouma; Maarten van den Buuse

doi:10.3390/biology12060799

Biology (May 2023)

A Rat Model of the Brain-Derived Neurotrophic Factor Val66Met Polymorphism Shows Attenuated Motivation for Alcohol Self-Administration and Diminished Propensity for Cue-Induced Relapse in Females

Emily J. Jaehne,
Elizabeth McInerney,
Ronan Sharma,
Shannyn G. Genders,
Elvan Djouma,
Maarten van den Buuse

Affiliations

Emily J. Jaehne: Department of Psychology, Counselling and Therapy, School of Psychology and Public Health, La Trobe University, Melbourne 3086, Australia
Elizabeth McInerney: Department of Microbiology, Anatomy, Physiology and Pharmacology, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne 3086, Australia
Ronan Sharma: Department of Psychology, Counselling and Therapy, School of Psychology and Public Health, La Trobe University, Melbourne 3086, Australia
Shannyn G. Genders: Department of Microbiology, Anatomy, Physiology and Pharmacology, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne 3086, Australia
Elvan Djouma: Department of Microbiology, Anatomy, Physiology and Pharmacology, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne 3086, Australia
Maarten van den Buuse: Department of Psychology, Counselling and Therapy, School of Psychology and Public Health, La Trobe University, Melbourne 3086, Australia

DOI: https://doi.org/10.3390/biology12060799
Journal volume & issue: Vol. 12, no. 6
p. 799

Abstract

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Brain-derived neurotrophic factor (BDNF) has been implicated in alcohol use disorder. The Val66Met polymorphism is a common variant of the BDNF gene (rs6265) which reduces activity-dependent BDNF release, and has been suggested as a risk factor for psychiatric disorders and substance use. Using an operant self-administration paradigm, this study aimed to investigate ethanol preference and ethanol seeking in a novel rat model of the BDNF Val66Met polymorphism, Val68Met rats. Male and female BDNF Val68Met rats of three genotypes (Val/Val, Val/Met and Met/Met) were trained to lever press for a 10% ethanol solution. There was no effect of Val68Met genotype on acquisition of stable response to ethanol or its extinction. Met/Met rats of both sexes had a slight, but significantly lower breakpoint during progressive ratio sessions while female rats with the Met/Met genotype demonstrated a lower propensity for reinstatement of responding to cues. There were no effects of Val68Met genotype on anxiety-like behaviour or locomotor activity. In conclusion, Met/Met rats showed lower motivation to continue to press for a reward, and also a decreased propensity to relapse, suggesting a possible protective effect of the Met/Met genotype against alcohol use disorder, at least in females.

Published in Biology

ISSN: 2079-7737 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: https://www.mdpi.com/journal/biology

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