Acute tramadol enhances brain activity associated with reward anticipation in the nucleus accumbens
Tramadol is an analgesic with monoamine reuptake inhibition and μ-opioid receptor activation. Although tramadol has been widely used for treatment of various pain conditions, there is controversy over the risk of abuse potential. We examined the effects of tramadol on the reward system in humans using functional magnetic resonance imaging (fMRI) to assess the potential of tramadol for drug abuse or dependence.
A randomized, double-blind, placebo-controlled, crossover study was conducted for 19 healthy adults under tramadol or placebo. In association with subjective mood questionnaires, monetary incentive delay (MID) task was performed to assess the neural response to reward anticipation during fMRI. Subjective mood measures and blood oxygenation level-dependent (BOLD) signal during gain and loss anticipation were compared between tramadol and placebo.
Tramadol significantly reduced anxiety (Z = − 2.513, p = 0.012) and enhanced vigor (Z = − 2.725, p = 0.006) compared with placebo. By Mood Rating Scale, tramadol provoked contented (Z = − 2.316, p = 0.021), relaxed (Z = − 2.236, p = 0.025), and amicable feelings (Z = − 2.015, p = 0.044) as well as increased alertness (Z = − 1.972, p = 0.049) and contentedness domains (Z = − 2.174, p = 0.030) compared with placebo. Several brain regions including nucleus accumbens (NAc) were activated during gain anticipation in the MID task under both tramadol and placebo. Tramadol increased the %BOLD signal change in NAc at +¥500 cue significantly more than the placebo (Z = − 2.295, p = 0.022).
Tramadol enhances the reward system and thereby may have abuse potential or precipitate drug abuse in human.
KeywordsDrug abuse fMRI Monetary incentive delay task Nucleus accumbens Reward system Tramadol
The authors are entirely responsible for the scientific content of this paper. We are thankful to the Clinical Imaging Center for Healthcare, Nippon Medical School, for their support. In particular, we thank Koji Nagaya, Megumi Hongo, Koji Kanaya, Masaya Suda, Minoru Sakurai, Satoe Aoyama, and Aiko Abe for their technical assistance with the MRI examinations and Michiyo Tamura for research assistance. We also thank Dr. Gerz for his English editing of the manuscript.
Compliance with ethical standards
All participants gave written informed consent, and the study was approved by the ethics committee of Nippon Medical School (approval number 226018).
Conflict of interest
The authors declare that they have no conflict of interest.
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