Abstract
Rationale and objective
Post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) are disorders of learning and memory that often occur comorbidly. Exposure to trauma-related cues can increase alcohol intake in PTSD patients that are using alcohol to self-medicate. The recurrence of anxiety symptoms with subsequent alcohol use may initiate a destructive cycle where stress and alcohol exposure impair the function of the prefrontal cortex (PFC). While the incidence of these disorders has steadily increased, current therapies and treatments often lack efficacy. Thus, investigation into the underlying neurocircuitry responsible for the establishment and maintenance of these disorders is necessary to develop novel treatment targets.
Methods
The present study examined the effects of ethanol exposure on the ability to create new learned associations around previously conditioned fear cues in a rat model. Animals were exposed to fear conditioning followed by chronic intermittent ethanol to translationally model trauma exposure followed by alcohol abuse. Optogenetics was used to inhibit the prelimbic (PrL) or infralimbic (IfL) cortex during fear memory reconsolidation, and fear behaviors were measured during subsequent extinction and spontaneous recovery tests.
Results and conclusion
Chronic ethanol exposure led to deficits in fear extinction learning and increased freezing during spontaneous recovery, both of which were prevented following inhibition of the PrL, but not the IfL, during memory reconsolidation. These results support the involvement of the PrL in fear learning and memory, and strongly suggest that the PrL could serve as a potential target for the treatment of the learning and memory deficits that occur following exposure to stress and alcohol.
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This work was supported by the National Institutes of Health (grant numbers R00AA020537 and R01AA024526) and the National Institute on Alcohol Abuse and Alcoholism (grant number 5T32AA007474).
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Smiley, C.E., McGonigal, J.T., Nimchuk, K.E. et al. Optogenetic manipulation of the prelimbic cortex during fear memory reconsolidation alters fear extinction in a preclinical model of comorbid PTSD/AUD. Psychopharmacology 238, 3193–3206 (2021). https://doi.org/10.1007/s00213-021-05935-3
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DOI: https://doi.org/10.1007/s00213-021-05935-3