Samantha G Malone1, Peggy S Keller1, Lindsey R Hammerslag1, Michael T Bardo2,3. 1. Department of Psychology, University of Kentucky, Lexington, KY, USA. 2. Department of Psychology, University of Kentucky, Lexington, KY, USA. mbardo@uky.edu. 3. Biomedical Biological Science Research Building, University of Kentucky, Room 447, 741 S. Limestone, Lexington, KY, 40536-0509, USA. mbardo@uky.edu.
Abstract
RATIONALE: Escalation of drug intake and craving are two DSM-5 hallmark symptoms of opioid use disorder (OUD). OBJECTIVES: This study determined if escalation of intake as modeled by long access (LgA) self-administration (SA) and craving measured by reinstatement are related. METHODS: Adult male and female Sprague-Dawley rats were trained to self-administer fentanyl across 7 daily 1-h short access (ShA) sessions, followed by 21 SA sessions of either 1- or 6-h duration (ShA or LgA). 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), and Experiment 2 assessed reinstatement induced by a drug-associated cue light. RESULTS: Females acquired fentanyl SA faster than males. When shifted to LgA sessions, LgA rats escalated fentanyl intake, but ShA rats did not; no reliable sex difference in the rate of escalation was observed. In extinction, compared to ShA rats, LgA rats initially responded less and showed less decay of responding across sessions. A priming injection of fentanyl induced reinstatement, with LgA rats reinstating more than ShA rats at the 30 µg/kg dose. Yohimbine (1 mg/kg) also induced reinstatement, but there was no effect of access group or sex. With cue-induced reinstatement, LgA females reinstated less than LgA males and ShA females. CONCLUSION: Among the different reinstatement tests assessed, escalation of fentanyl SA increased only drug-primed reinstatement, suggesting a limited relationship between escalation of drug intake and craving (reinstatement) for OUD.
RATIONALE: Escalation of drug intake and craving are two DSM-5 hallmark symptoms of opioid use disorder (OUD). OBJECTIVES: This study determined if escalation of intake as modeled by long access (LgA) self-administration (SA) and craving measured by reinstatement are related. METHODS: Adult male and female Sprague-Dawley rats were trained to self-administer fentanyl across 7 daily 1-h short access (ShA) sessions, followed by 21 SA sessions of either 1- or 6-h duration (ShA or LgA). 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), and Experiment 2 assessed reinstatement induced by a drug-associated cue light. RESULTS: Females acquired fentanyl SA faster than males. When shifted to LgA sessions, LgA rats escalated fentanyl intake, but ShA rats did not; no reliable sex difference in the rate of escalation was observed. In extinction, compared to ShA rats, LgA rats initially responded less and showed less decay of responding across sessions. A priming injection of fentanyl induced reinstatement, with LgA rats reinstating more than ShA rats at the 30 µg/kg dose. Yohimbine (1 mg/kg) also induced reinstatement, but there was no effect of access group or sex. With cue-induced reinstatement, LgA females reinstated less than LgA males and ShA females. CONCLUSION: Among the different reinstatement tests assessed, escalation of fentanyl SA increased only drug-primed reinstatement, suggesting a limited relationship between escalation of drug intake and craving (reinstatement) for OUD.
Authors: Marilyn E Carroll; Andrew D Morgan; Wendy J Lynch; Una C Campbell; Nancy K Dess Journal: Psychopharmacology (Berl) Date: 2002-03-27 Impact factor: 4.530
Authors: Samuel J Harp; Mariangela Martini; Will Rosenow; Larry D Mesner; Hugh Johnson; Charles R Farber; Emilie F Rissman Journal: Physiol Behav Date: 2021-10-26