Curcumin, demethoxycurcumin and bisdemethoxycurcumin differentially inhibit morphine's rewarding effect in rats.
BACKGROUND
Recent animal studies reported that curcumin, the active constituent of Curcuma longa, has several central actions and may attenuate morphine tolerance.


OBJECTIVE
In the present study, we utilized the intracranial self-stimulation (ICSS) paradigm to examine the effects of the commercially available curcuminoid mixture and each one of its components, individually, on brain stimulation reward and on the reward-facilitating effect of morphine.


METHODS
Male Sprague-Dawley rats were implanted with an electrode into the medial forebrain bundle and trained to respond for electrical stimulation using a rate-frequency paradigm. In the first study, rats were injected with graded doses either of the curcuminoid mixture, or curcumin I, or II, or III. In the second study, we examined whether a low dose of the curcuminoid mixture or each individual curcumin analogue composing it could counteract the reward-facilitating effect of morphine.


RESULTS
At low doses, both the curcuminoid mixture and curcumin I did not affect brain stimulation reward, whereas, higher doses increased ICSS thresholds. Curcumin II and curcumin III did not affect brain stimulation reward at any doses. Subthreshold doses of the curcuminoid mixture and curcumin I inhibited the reward-facilitating effect of morphine.


CONCLUSIONS
Both the curcuminoid mixture and curcumin I lack hedonic properties and moderate the reward-facilitating effect of morphine. Our data suggest that curcumin interferes with brain reward mechanisms responsible for the expression of the acute reinforcing properties of opioids and provide evidence that curcumin may be a promising adjuvant for attenuating morphine's rewarding effects in patients who are under long-term opioid therapy.
Laboratory of Behavioral Neuroscience, Department of Psychology, School of Social Sciences, University of Crete, 74100, Rethymno, Crete, Greece.
Vicky
V
Katsidoni
Polyxeni
P
Alexiou
Marilena
M
Fotiadou
Maria
M
Pelecanou
Marina
M
Sagnou
George
G
Panagis
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology; D036381:Diarylheptanoids; D004558:Electric Stimulation; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects*; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D012653:Self Stimulation
D000701:Analgesics, Opioid; D036381:Diarylheptanoids; C034786:bisdemethoxycurcumin; C475935:curcumin III; D009020:Morphine; D003474:Curcumin; C050229:demethoxycurcumin