IntA fentanyl self-administration

Once rats acquired fentanyl self-administration, they were given extended, 24-h access to fentanyl for 10 consecutive days under an IntA procedure recently developed by Dave Roberts and colleagues (Zimmer et al. 2012). This procedure has already been used fairly extensively with psychostimulants since it readily induces features of an addicted phenotype, including the development of a marked increase in motivation for the drug and vulnerability to relapse as assessed following abstinence (Zimmer et al. 2012; Calipari et al. 2013, 2014, 2015; Calipari and Jones 2014; Kawa et al. 2016; Allain et al. 2017, 2018; Singer et al. 2017; Venniro et al. 2018; Kawa and Robinson 2019; Gueye et al. 2019; Nicolas et al. 2019; Allain and Samaha 2019). Similar findings have been reported for InA opioid self-administration, including fentanyl (Fragale et al. 2020; Martin et al. 2020; O’Neal et al. 2020). With this procedure, rats had unrestricted, fixed-ratio 1, access to rapidly delivered infusions of fentanyl (~ 1 s) during 5-min trials that initiated every 30 min around the clock. As with the training phase, each trial initiated with the extension of the left lever into the operant chamber and responses on this lever during each trial were reinforced under a fixed-ratio 1 schedule; each infusion was also paired with the sound of the pump and the illumination of the stimulus light above the lever. However, in contrast to training sessions, no priming infusions were administered, and no time-outs were imposed during IntA sessions. The left lever retracted at the end of each trial; responses on the right lever were recorded throughout the 24-h sessions. Sessions continued daily for 10 days. Incidences of self-injurious gnawing were managed using topically applied antibiotic cream and/or systemically administered antibiotic (gentamicin, 5.5 mg/kg, i.v.).