TY - JOUR
T1 - Brain-derived neurotrophic factor (BDNF) determines a sex difference in cue-conditioned alcohol seeking in rats
AU - Hogarth, Samuel J.
AU - Jaehne, Emily J.
AU - van den Buuse, Maarten
AU - Djouma, Elvan
N1 - Funding Information:
These studies were supported by a Senior Research Fellowship of the National Health and Medical Research Council (Australia) to MvdB. This funding source had no role in study design, the collection, analysis and interpretation of data, in the writing of this report, or in the decision to publish it.
Publisher Copyright:
© 2017
PY - 2018/2/26
Y1 - 2018/2/26
N2 - Alcohol use disorder is a detrimental addictive disease that develops through prolonged ethanol exposure and regular intoxication. However, the changes in the underlying neurobiology leading to alcohol addiction remain unclear. Brain-Derived Neurotrophic Factor (BDNF) is implicated in substance abuse disorders including alcoholism. As the vast majority of previous animal model studies have concentrated on males only, the aim of this study was to determine whether endogenous BDNF mediates alcohol seeking in a sex-specific manner. We used an operant self-administration paradigm where the animals were trained in operant chambers to self-administer a 10% ethanol solution, and compared male and female BDNF heterozygous (HET) and wildtype (WT) rats. Over several weeks, the animals progressed through acquisition, progressive ratio, extinction, and reinstatement phases. There were no significant sex or genotype differences in the number of alcohol-paired lever presses during acquisition, progressive ratio and extinction. However, a significant difference between male and female WT rats following alcohol-primed reinstatement was completely absent in BDNF HET rats suggesting a role of BDNF in sex differences in alcohol seeking after abstinence. Female BDNF HET rats showed significantly higher number of alcohol-paired lever presses during reinstatement than female WT controls. These findings suggest that BDNF regulatory pathways are involved in sex differences in reinstatement of alcohol intake and emphasize the need to include both male and female animals to explore sex-specific interactions in addiction neurocircuitry.
AB - Alcohol use disorder is a detrimental addictive disease that develops through prolonged ethanol exposure and regular intoxication. However, the changes in the underlying neurobiology leading to alcohol addiction remain unclear. Brain-Derived Neurotrophic Factor (BDNF) is implicated in substance abuse disorders including alcoholism. As the vast majority of previous animal model studies have concentrated on males only, the aim of this study was to determine whether endogenous BDNF mediates alcohol seeking in a sex-specific manner. We used an operant self-administration paradigm where the animals were trained in operant chambers to self-administer a 10% ethanol solution, and compared male and female BDNF heterozygous (HET) and wildtype (WT) rats. Over several weeks, the animals progressed through acquisition, progressive ratio, extinction, and reinstatement phases. There were no significant sex or genotype differences in the number of alcohol-paired lever presses during acquisition, progressive ratio and extinction. However, a significant difference between male and female WT rats following alcohol-primed reinstatement was completely absent in BDNF HET rats suggesting a role of BDNF in sex differences in alcohol seeking after abstinence. Female BDNF HET rats showed significantly higher number of alcohol-paired lever presses during reinstatement than female WT controls. These findings suggest that BDNF regulatory pathways are involved in sex differences in reinstatement of alcohol intake and emphasize the need to include both male and female animals to explore sex-specific interactions in addiction neurocircuitry.
KW - Alcohol seeking
KW - Brain-derived neurotrophic factor
KW - Extinction
KW - Reinstatement
KW - Sex differences
UR - http://www.scopus.com/inward/record.url?scp=85034629554&partnerID=8YFLogxK
U2 - 10.1016/j.bbr.2017.11.019
DO - 10.1016/j.bbr.2017.11.019
M3 - Article
C2 - 29158111
AN - SCOPUS:85034629554
SN - 0166-4328
VL - 339
SP - 73
EP - 78
JO - Behavioural Brain Research
JF - Behavioural Brain Research
ER -