Author ORCID Identifier

Year of Publication


Degree Name

Master of Science (MS)

Document Type

Master's Thesis


Arts and Sciences



First Advisor

Dr. Michael T. Bardo


Escalation of intake and craving are two DSM-5 hallmark symptoms of opioid use disorder (OUD). Objectives: This study determined if escalation measured by long access (LgA) self-administration and craving measured by reinstatement are related. Adult male and female Sprague-Dawley rats were trained to self-administer (SA) fentanyl across 7 daily 1-h sessions, followed by 21 SA sessions of either 1- or 6-h duration. Assignment to short access (ShA) and long access (LgA) groups was randomly determined for both males and females. Following 14 1-h extinction sessions, Experiment 1 assessed reinstatement induced by either fentanyl (10 or 30 μg/kg) or yohimbine (1 or 2 mg/kg), while Experiment 2 assessed reinstatement induced by a drug-associated cue light. Females acquired fentanyl SA faster than males and self-administered more than males throughout escalation. In extinction, compared to ShA rats, LgA rats initially responded less and showed less decay of responding across sessions. A fentanyl prime induced reinstatement, with LgA rats reinstating more than ShA rats at the 30 μg/kg dose; this effect of was specific to males. Yohimbine (1 mg/kg) also induced reinstatement, but there was no effect of access group or sex. With cue-induced reinstatement, LgA females responded less than LgA males and ShA females; the reduced fentanyl seeking to a cue in LgA females may reflect a general decrease in behavior, as this group also showed suppressed locomotor activity in a different context. Among the different reinstatement tests assessed, escalation of fentanyl SA in the LgA group increased only drug-primed reinstatement and only in males, suggesting a limited relationship between escalation of intake and craving (reinstatement) for OUD.

Digital Object Identifier (DOI)