Abstract
Post-traumatic stress disorder (PTSD) is initiated by traumatic-stress exposure and manifests into a collection of symptoms including increased anxiety, sleep disturbances, enhanced response to triggers, and increased sympathetic nervous system arousal. PTSD is highly co-occurring with alcohol use disorder. Only some individuals experiencing traumatic stress develop PTSD and a subset of individuals with PTSD develop co-occurring alcohol use disorder. To investigate the basis of these individual responses to traumatic stress, single prolonged stress (SPS) a rodent model of traumatic stress was applied to young adult female rats. Individual responses to SPS were characterized by measuring anxiety-like behaviors with open field and elevated plus maze tests. Rats were then allowed to drink ethanol under an intermittent two bottle choice procedure for 8 weeks, and ethanol consumption was measured. An artificial intelligence algorithm was built to predict resilient and vulnerable individuals based on data from anxiety testing and ethanol consumption. This model was implemented in a second cohort of rats that underwent SPS without ethanol drinking to identify resilient and vulnerable individuals for further study. Analysis of neuropeptide Y (NPY) levels and expression of its receptors Y1R and Y2R mRNA in the central nucleus of the amygdala (CeA), basolateral amygdala (BLA), and bed nucleus stria terminalis (BNST) were performed. Results demonstrate that resilient rats had higher expression of Y2R mRNA in the CeA compared with vulnerable and control rats and had higher levels of NPY protein in the BNST compared to controls. The results of the study show that an artificial intelligence algorithm can identify individual differences in response to traumatic stress which can be used to predict subsequent ethanol drinking, and the NPY pathway is differentially altered following traumatic stress exposure in resilient and vulnerable populations. Understanding neurochemical alterations following traumatic-stress exposure is critical in developing prevention strategies for the vulnerable phenotype and will help further development of novel therapeutic approaches for individuals suffering from PTSD and at risk for alcohol use disorder.
Highlights
Post-traumatic stress disorder (PTSD) is a debilitating condition initiated by traumatic stress exposure and is marked by a constellation of symptoms including indelible memories and heightened sympathetic nervous system arousal (Atwoli et al, 2015)
Analysis of mean ethanol consumed and mean ethanol preference during weeks 6–8 for each rat showed that vulnerable rats consumed significantly more ethanol than resilient rats [Figure 7C, t(9) = 4.197, P = 0.0023] and likewise, vulnerable rats had a greater preference for ethanol than resilient rats 6–8 [Figure 7D, t(9) = 2.759, P = 0.0221]. These results demonstrate that the unsupervised machine learning algorithm successfully identified two populations of rats, labeled as ‘resilient’ and ‘vulnerable,’ that were phenotypically different in terms of anxiety-like and ethanol drinking behaviors
The current study investigated individual responses to traumatic stress exposure and a potential neurochemical mechanism underlying these differences
Summary
Post-traumatic stress disorder (PTSD) is a debilitating condition initiated by traumatic stress exposure and is marked by a constellation of symptoms including indelible memories and heightened sympathetic nervous system arousal (Atwoli et al, 2015). In the United States 60% of males and 50% of females are exposed to at least one traumatic stress during their lifetime (Kessler et al, 1995). Of these individuals only 15– 30% go on to develop PTSD (Kessler et al, 1995). American veterans diagnosed with PTSD are 3–4.5 times more likely to have a co-occurring AUD (Carter et al, 2011; Seal et al, 2011). PTSD usually precedes the development of an AUD, and when PTSD and AUD present together, individuals have worse outcomes and report more severe symptomologies of both disorders compared to individuals with only PTSD or AUD (Carter et al, 2011; Seal et al, 2011)
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