The effects of chronic intermittent ethanol exposure on fear conditioning in rats: an investigation of the comorbidity of PTSD and AUD

Numerous studies, in both animal models and humans, have found direct interconnections between anxiety disorders and alcohol use disorder (AUD). Post-traumatic stress disorder (PTSD) and AUD are two such disorders which express extremely high rates of comorbidity that results in a worsened prognosis for each. Despite the high rates of each of these disorders, little is known about the neural substrates responsible for the frequent co-occurrence of these disorders. In particular, it is unknown whether or not AUD develops as a means of self-medication of PTSD symptoms or if there is an underlying mechanism of vulnerability to both disorders. To this end, we aimed to perform and unbiased study of a possible AUD-PTSD comorbidity rat model, expanding on an experiment previously performed in mice. Similar to the mouse study, we tested the effect of chronic intermittent ethanol (CIE), a model of alcohol dependence, on fear conditioning, a model of fear learning that engages circuits that are dysregulated in PTSD, in male Long Evans rats. We further expanded this research by looking at the effects of this exposure on subsequent ethanol drinking behaviors, using a two-bottle choice paradigm. We hypothesized that we would validate previous findings by seeing alterations of fear extinction in CIE exposed rats, similar to symptoms of PTSD patients. Moreover, we predicted that the exposure to both CIE and fear conditioning would result in increased long-term drinking in comparison to CIE or fear conditioning alone, as seen in PTSD/AUD comorbid patients. As predicted, dysregulation of fear extinction was observed. Unexpectedly, we also noted alterations in acquisition of fear and spontaneous recovery of fear. We also found that rats exposed to CIE (with and without fear conditioning) exhibited increased binge-like drinking in comparison to those exposed to air; those exposed to CIE and fear trended to drink more than cohorts exposed to just one of these conditions. Together, these results are consistent with the notion that these animal models may recapitulate salient features of comorbid PTSD and AUD and that they may prove useful in elucidating neural adaptations that promotes these disorders.

Grantor dc:publisher

Wake Forest University

Year dc:date.issued

2018

Author dc:creator

• McMullen, Nathan Paul

• Alcohol Addiction

Language dc:language.iso

en

Handle dc:identifier.uri

http://hdl.handle.net/10339/90717

OAI identifier oai:identifier

oai:wakespace.lib.wfu.edu:10339/90717