Severe deficit in brain reward function associated with fentanyl withdrawal in rats.
BACKGROUND
During the last decade, there has been a strong increase in the use of the mu-opioid receptor agonist fentanyl. The aim of these studies was to investigate the effects of fentanyl withdrawal on brain reward function and somatic withdrawal signs.


METHODS
Fentanyl and saline were chronically administered via minipumps. An 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
The opioid receptor antagonist naloxone induced a dose-dependent elevation in brain reward thresholds and somatic withdrawal signs in fentanyl-treated rats. Discontinuation of fentanyl administration resulted in a time-dependent elevation of brain reward thresholds and somatic withdrawal signs.


CONCLUSIONS
These findings indicate that fentanyl withdrawal is associated with affective and somatic withdrawal signs. The severity of the deficit in brain reward function in this animal model suggests that affective fentanyl withdrawal symptoms may be a strong deterrent to abstinence.
Bruijnzeel
Adrie W
AW
Department of Psychiatry, College of Medicine, University of Florida, Gainesville, Florida 32610-0244, USA. awbruijn@psychiatry.ufl.edu
Lewis
Ben
B
Bajpai
Lakshmi K
LK
Morey
Timothy E
TE
Dennis
Donn M
DM
Gold
Mark
M
D000339:Affect / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005283:Fentanyl / Q000633:toxicity*; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects / Q000503:physiopathology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009293:Opioid-Related Disorders / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000502:physiology; D012201:Reward; D012653:Self Stimulation / Q000187:drug effects* / Q000502:physiology; D012684:Sensory Thresholds; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D009270:Naloxone; D005283:Fentanyl