Gustavo D. Hernández-Luciano¹, Y. Rivera-Escobales¹ , K. Carrasquillo-Carrión⁴, Y. M. Cantres-Rosario⁴,

A. Rodríguez-De Jesús⁵, Y. Castillo-Ocampo¹ , C. Suarez-Gómez¹ , L. Sambolín-Escobales¹, M. Colón-Romero¹ ,

A. Roche-Lima⁴ , L. M. Meléndez-Aponte²,³,⁵, J. Porter¹

1 Ponce Health Sciences University, Ponce Research Institute, Ponce, Puerto Rico

2 University of Puerto Rico Medical Sciences Campus

3 Department of Microbiology and Medical Zoology

4 Comprehensive Cancer Center, San Juan, PR

5 Center for Collaborative Research in Health Disparities (CCHRD) Research Infrastructure Core, San Juan, PR


One diagnostic criterion for post-traumatic stress disorder (PTSD) is exposure to a traumatic event.

However, experiencing a traumatic event will not necessarily result in PTSD. The molecular

mechanisms that underlie protection against traumatic sequels remain unclear. The single

prolonged stress (SPS) is an animal model of PTSD recently develop that induces a PTSD-like

behavior in rodents 7 days after exposure to three different stressors. This model consisting of

restraint stress, forced swim test and ether-induced loss of consciousness has proven to induce

behavioral and molecular characteristics similar to humans with PTSD. Still, similar to humans, rats

exposed to SPS show variability in their behavior. Not all rats exposed to SPS end up developing a

PTSD-like phenotype. It should be noted that although the prevalence of PTSD is twice in women

than men, few studies include female rats in their research. The few studies including female rats

suggest that they are not sensitive to the effects of SPS. Thus, in this study we aim to investigate the

molecular mechanisms underlying the variability in behavior in SPS exposed animals. To this end,

we exposed male and female Sprague Dawley rats (p60) to the SPS. Seven days after we trained

the animals in fear conditioning. Results showed variability in the ability to extinguish the fear

memory. From a pool of 8 male and female SPS exposed animals’ half of them presented

impairment in fear memory extinction. The other half were able to recall the extinction memory.

Since the medial prefrontal cortex has been reported to have a role in fear memory acquisition and

extinction, we collected tissue punches from the prelimbic and infralimbic cortex for proteomic

analysis of membrane associated proteins of those animals with impaired or enhanced fear

memory extinction. Analysis of differentiated abundant proteins across the medial prefrontal cortex

of female and male rats reveal that the infralimbic cortex of female rats had the higher expression

of proteins in comparison to the infralimbic cortex of male rats. We found only two common proteins

between sex. These results suggest sex differences at the molecular level in the infralimbic cortex

associated with impaired extinction of the conditioned fear response.

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