Colin MacKenzie M.D.
January 10, 2021

Gender Specific Responses To Alcohol Withdrawal and Possible Neuronal Correlates


The research literature suggests that men and women experience alcohol withdrawal symtpoms differently with women being more suspectible to symptoms of depression and relapse caused by depressive symptoms, while men tend to relapse more within the context of other alcohol users.  This gender difference may be due to a certain neuropeptide called somatostatin (SST) and specific brain circuits that are susceptible to the influence of alcohol. 

In both human and animal studies, correlates between alcohol use disorder, depressive disorders, and relapse triggers have been identified.  This study set out to see if SST and SST neurons could be the reason why alcohol use disorder, depression, and the differences in relapse behavior between men and women appear to be associated with one another.  Nicole Crowley and colleagues also conducted this study to determine the differences in withdrawal symptoms and relapse behavior between the genders, and to identify the neuronal mechanisms responsible for this behavior.


The researchers induced forced alcohol abstinence on mice by creating control and test groups. The mice in test groups were given free access to two bottles containing water and the other containing alcohol. The concentration of alcohol was increased gradually over 42 days, and then the provision was stopped entirely. The control group was given water only from the two bottles during the study time frame. After one week of forced abstention, the mice underwent a series of behavioral tests to identify features of depression and anxiety. Then, neuronal assays were performed to look for changes in brain activity in certain brain circuits.


The results showed a different pattern of neuronal signals between male and female abstinent mice. Both depicted the features of depression, but the behaviors employed to cope with the negative emotions were different and involved different areas of the brain. Female forced abstinent mice showed lower overall neural activity levels in areas of the brain used to co-ordinate stress signals to deal with threats effectively. They also showed a significant increase in plasticity and activity level of the neurons responsible for releasing the hormone somatostatin compared to the male counterpart.


It was concluded from the study that females may be more predisposed to the development of several neuropsychiatric disorders including MDD, anxiety, post-traumatic stress disorder (PTSD), and stress-mediated relapse in the context of alcohol use. The findings are based on differences in neural circuitry and plasticity that are susceptible to change during and after chronic alcohol consumption which differed from the findings in males. However, this study was performed on mice, and making correlations with humans can be difficult.  

Based on these conclusions, effective treatment modalities may be implemented to prevent alcohol relapse among females due to depressive illness by targeting the specific neurons and hormonal analogs with pharmaceuticals.

Crowley Nicole A. et al. Forced Abstinence From Alcohol Induces Sex-Specific Depression-Like Behavioral and Neural Adaptations in Somatostatin Neurons in Cortical and Amygdalar Regions. Front. Behav. Neurosci., 27 May 2020 | https://doi.org/10.3389/fnbeh.2020.00086