Roberto J Morales-Silva, Ursula Gelpi-Domínguez, Joshua Perez-Torres, Yobet Perez-Perez, Genesis Rodriguez-

Torres , Marian Sepulveda-Orengo

Department of Basic Sciences, Ponce Health Sciences University-School of Medicine/Ponce Research Institute,

Ponce, Puerto Rico 00732, USA

Generally, Post-Traumatic Stress Disorder (PTSD) and Substance Use Disorder (SUD) are studied independently in preclinical studies, although they can occur concurrently in patients and in fact, PTSD patients exhibit higher rates of SUD. Exposure to stressful or traumatic events can lead to the development of PTSD, and stress has been associated with a higher probability of relapse.

Previous studies have shown that modified single prolonged stress reduces cocaine selfadministration in rats, as well as a reduced cue-induced reinstatement of cocaine seeking behavior, without any effects on acquisition and extinction of cocaine self-administration. These studies used a short-access cocaine self-administration paradigm, and the effects of chronic stress on extended-access cocaine self-administration remain to be studied. Our objective is to determine the effects of chronic stress on cocaine seeking behavior in male and female rats. We hypothesize that unescapable footshocks prior cocaine self-administration will increase cocaine seeking behavior in both sexes. To test this hypothesis, we used unescapable footshocks for a period of 5 days at an intensity of 0.50mA (presented randomly), followed by 6-hour sessions of extended-access cocaine self-administration for 10 days, and a 30 day forced abstinence period.

Subsequently, we examined conditioned stimulus- and cocaine-induced cocaine-seeking behavior. Our data show that unescapable footshocks prior cocaine acquisition increases cocaine-primed memory retrieval after withdrawal in male and female rats. Interestingly, only female rats show an increase in cue-induced cocaine seeking behavior in the stress group, compared with the control group. Furthermore, preliminary data show that the stress group exhibits an increase in motivation for drug-seeking behavior in a fixed ratio 3 schedule of selfadministration sessions, compared with control group. These results suggest that chronic stress prior cocaine exposure increases the reinforcing effects of cocaine after forced abstinence in male and female rats, as well as the compulsivity of cocaine seeking behavior.

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