Mahdi Abdallah

Introduction. Post-traumatic stress disorder (PTSD) is characterized by avoidance of trauma-associated stimuli and amygdala hyperreactivity and is highly co-morbid with alcohol use disorder (AUD).¹ The relationship between the frequency of childhood physical, sexual and emotional abuse and PTSD showed a high lifetime prevalence on alcohol abuse.² Studies have found that Oxytocin (OT) plays an active role in adaptive stress induced responses and integrally protects the synaptic plasticity and memory of the hippocampus of mice by counteracting the action of corticosterone (CORT)-induced apoptosis.³ Other studies conveyed that stress and anxiety related behaviors, that are shown in PTSD and AUD, are elicited by reducing oxytocin-induced GABAergic transmission in the central amygdala(CeA).⁴ These findings suggest that OT may be a potential therapy for the comorbidity of PTSD/AUD. Methods. The effects of oxytocin on hippocampal neurons with CORT only vs neurons with CORT + OT were examined and a TUNEL Assay was used to determine the number of apoptotic DNA fragmentations in each. Additionally, a Forced Swim Test (FST) and Miniature Inhibitory Synaptic Currents (mIPSC) of the CeA was measured in isolation induced depressed mice without treatment vs isolation induced depressed mice that were treated with oxytocin.⁴ The isolated mice were subjected to 5 weeks of continuous isolation. The mIPSC of the CeA indicated the function of the amygdala in response to stress and the immobility time indicated a sign of hopelessness that equates to depression. Results. The number of TUNEL-positive cells was significantly higher in CORT-treated neurons [P < 0.05] than in those treated with vehicle, whereas co- treatment with OT caused a dramatic decrease in the number of apoptotic cells.³ In the amygdala, findings showed a significant decrease in immobility time in the group treated with OT compared to the other groups and displayed a significant increase in mIPSC of the CeA in isolated induced depressed mice.⁴ Conclusions. Patients suffering from co-occurring PTSD/AUD can benefit from oxytocin therapy due to its physiological role in the development of brain and its pharmacological value in treating stress-related disorders.³ Aside from OT’s therapeutic potential, studies imply that modulation of OT Receptor signaling and expression in the amygdala is a promising target for the treatment of PTSD/AUD.⁴ Developing this knowledge and continuing research on OT’s effect on the hippocampus and amygdala would help substantially alleviate PTSD in major target groups (i.e. veterans) and reduce the chance of developing AUD.

1. Weera MM, Schreiber AL, Avegno EM, Gilpin NW. The role of central amygdala corticotropin-releasing factor in predator odor stress-induced avoidance behavior and escalated alcohol drinking in rats. Neuropharmacology. 2020;166:107979. doi:10.1016/j.neuropharm.2020.107979.
2. Gilpin NW, Weiner JL. Neurobiology of comorbid post-traumatic stress disorder and alcohol-use disorder. Genes, Brain and Behavior. 2016;16(1):15-43. doi:10.1111/gbb.12349.
3. Latt HM, Matsushita H, Morino M, et al. Oxytocin Inhibits Corticosterone-induced Apoptosis in Primary Hippocampal Neurons. Neuroscience. 2018;379:383-389. doi:10.1016/j.neuroscience.2018.03.025.
4. Han RT, Kim Y-B, Park E-H, et al. Long-Term Isolation Elicits Depression and Anxiety-Related Behaviors by Reducing Oxytocin-Induced GABAergic Transmission in Central Amygdala. Frontiers in Molecular Neuroscience. 2018;11. doi:10.3389/fnmol.2018.00246.