TY - JOUR
T1 - 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
AU - Jaehne, Emily J.
AU - McInerney, Elizabeth
AU - Sharma, Ronan
AU - Genders, Shannyn G.
AU - Djouma, Elvan
AU - van den Buuse, Maarten
N1 - Funding Information:
These studies were supported in part by a Research Focus Area grant from La Trobe University, internal student support from the School of Psychology and Public Health and the School of Agriculture, Biomedicine and Environment, La Trobe University, and an Ideas Grant from the National Health and Medical Research Council of Australia (APP1187652).
Publisher Copyright:
© 2023 by the authors.
PY - 2023/6
Y1 - 2023/6
N2 - 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.
AB - 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.
KW - alcohol
KW - brain-derived neurotrophic factor
KW - breakpoint
KW - operant
KW - relapse
KW - Val66Met
UR - https://www.scopus.com/pages/publications/85163713709
U2 - 10.3390/biology12060799
DO - 10.3390/biology12060799
M3 - Article
C2 - 37372084
AN - SCOPUS:85163713709
SN - 2079-7737
VL - 12
JO - Biology
JF - Biology
IS - 6
M1 - 799
ER -
SDG 3 Good Health and Well-being