The effects of buprenorphine on fentanyl withdrawal in rats.
BACKGROUND
Fentanyl is a potent mu-opioid receptor agonist that is widely used for the treatment of severe chronic pain. Discontinuation of fentanyl administration has been shown to induce a negative emotional state.


OBJECTIVE
The aim of the present studies was to investigate the effects of the partial mu-opioid receptor agonist buprenorphine on the negative emotional state associated with precipitated and spontaneous fentanyl withdrawal in rats.


METHODS
Fentanyl and saline were chronically administered via osmotic minipumps. A discrete-trial intracranial self-stimulation procedure was used to provide a measure of brain reward function. Somatic signs were recorded from a checklist of opioid abstinence signs.


RESULTS
Naloxone induced a deficit in brain reward function in rats chronically treated with fentanyl. Buprenorphine dose-dependently prevented the naloxone-induced deficit in brain reward function. Discontinuation of fentanyl administration was also associated with a deficit in brain reward function. After explantation of the minipumps, the administration of buprenorphine induced a potentiation of brain reward function in the fentanyl-withdrawing rats, but did not affect brain reward function of saline-treated control rats. Buprenorphine prevented the somatic withdrawal signs associated with spontaneous fentanyl withdrawal and attenuated the somatic signs associated with precipitated fentanyl withdrawal.


CONCLUSIONS
Buprenorphine prevents affective and somatic fentanyl withdrawal signs. Moreover, buprenorphine is rewarding in rats previously exposed to fentanyl, but not in opioid-naïve rats. This pattern of results suggests that buprenorphine may be an effective treatment for the anhedonic-state associated with fentanyl withdrawal, but further study of buprenorphine's abuse potential is warranted.
Bruijnzeel
Adrie W
AW
Department of Psychiatry, McKnight Brain Institute, College of Medicine, University of Florida, 100 S. Newell Dr., 100256, Gainesville, FL 32610-0244, USA. awbruijn@psychiatry.ufl.edu
Marcinkiewcz
Catherine
C
Isaac
Shani
S
Booth
Matthew M
MM
Dennis
Donn M
DM
Gold
Mark S
MS
D000701:Analgesics, Opioid; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002047:Buprenorphine / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004644:Emotions / Q000187:drug effects*; D005283:Fentanyl; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000187:drug effects* / Q000378:metabolism; D012201:Reward; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D013997:Time Factors
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009294:Narcotics; D017450:Receptors, Opioid, mu; D009270:Naloxone; D002047:Buprenorphine; D005283:Fentanyl