Stress, Predictability, and Oral Fentanyl Self-Administration in Female and Male Rats

Abstract

Abstract : This experiment examined the relationship between stress and drug self-administration (SA) in an animal model. Specifically, the effects of predictable and unpredictable footshock stress on oral fentanyl (50 microgram/ml) consumption were examined in 12 female and 12 male Wistar rats using an operant conditioning paradigm. Female rats self-administered significantly greater amounts of fentanyl than did male rats and male rats exhibited more withdrawal behaviors following naloxone challenge. Predictability of a stressor was accompanied by significantly greater fentanyl SA, particularly for female rats. During relapse, animals exposed to predictable stress self-administered significantly less fentanyl during relapse stressor exposure than they did during the testing phase of the experiment. However, animals exposed to unpredictable stress self-administered similar amounts of fentanyl during relapse as they did during the testing phase. In addition, corticosterone levels were positively correlated with fentanyl SA Taken together, these results indicate that sex plays an important role inthe initiation, maintenance, and relapse of drug-taking behavior by rats. In addition, these findings suggest that female rats either are more sensitive to the nonpharmacologic variable of predictability or are more sensitive to the drug predictable stress interaction with regard to opiate SA. If these findings hold with clinical populations, then women and men may need different treatment approaches to opiate abuse.