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Studies of Continuous Lorcaserin Plus Buprenorphine in Rat Fentanyl Self‐Administration
Author(s) -
Merritt Christina,
Stutz Sonja,
Fox Robert,
Anastasio Noelle,
Moeller F. Gerard,
Cunningham Kathryn
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.06828
Subject(s) - buprenorphine , medicine , fentanyl , opioid , pharmacology , agonist , dosing , hydromorphone , heroin , anesthesia , opioid use disorder , naltrexone , drug , receptor
Aims Opioid overdose deaths and the rise in problematic opioid use patterns that indicate the development of opioid use disorder ( OUD ) have reached crisis levels in the United States. Medication‐assisted treatment ( MAT ) with therapeutics such as the partial μ‐opioid receptor agonist buprenorphine mitigate withdrawal, reduce mortality, and reduce intake of abused opioids (e.g., fentanyl, heroin). Still, the opioid epidemic has crystalized the need to identify adjunctive therapeutics to substantially improve the odds of successful recovery. In the present study, we tested the hypothesis that treatment with the FDA‐approved, 5‐HT 2C R agonist lorcaserin (Belviq ® ), previously shown to reduce opioid intake in the preclinical self‐administration ( SA ) model, may serve as an efficacious adjunct to suppress opioid intake and/or prevent escalation of opioid use after cessation of MAT. We employed osmotic minipumps to chronically administer buprenorphine and/or lorcaserin to achieve stable levels and mimic a clinical dosing regimen. Methods Male Sprague‐Dawley rats (n=34) were implanted with osmotic minipumps [sham, lorcaserin (1 mg/kg/day), buprenorphine (3 mg/kg/day), or the combination] following stable acquisition of fentanyl self‐administration. Rats resumed fentanyl self‐administration for 10 days and were then monitored for an additional ten days after removal of osmotic pumps. During this phase, the efficacy of acute lorcaserin (1 mg/kg) to impact fentanyl intake was evaluated. Results Chronic treatment with buprenorphine or the combination, but not lorcaserin alone, attenuated fentanyl intake relative to sham‐operated rats [F 3,30 =15.3, p <0.05]. Acute treatment with lorcaserin attenuated fentanyl intake relative to saline‐treated rats [F 1,12 =51.81, p <0.05]. Conclusions The efficacy of acute lorcaserin to suppress opioid intake extended to the illicit opioid fentanyl. Further, chronic buprenorphine, with or without lorcaserin, resulted in sustained inhibition of fentanyl intake. Taken together, these studies provide support for further interrogation of the efficacy or lorcaserin as a viable adjunct pharmacotherapy for MAT. Support or Funding Information Supported by the NIDA U54 DA038999