Samuel Turton, Peter C T Hawkins, Christopher Muller-Pollard, Evangelos Zois, Patricia Conrod, Fernando Zelaya, Mitul A Mehta
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引用次数: 0
Abstract
Rationale: It is hypothesised that modulation of striatal dopaminergic signalling plays a key role in the rewarding effects of opioids. The monetary incentive delay (MID) task is a functional magnetic resonance imaging (fMRI) paradigm used to investigate striatal responses, which may reflect striatal dopamine release, during the anticipation of a financial reward.
Objectives: We hypothesised that fentanyl would modulate striatal MID task Blood Oxygenation Level Dependent (BOLD) responses, reflecting opioidergic modulation of striatal dopaminergic signalling.
Methods: 24 right-handed males who undertook four MRI scanning sessions, during which they completed an MID task 15 min after receiving an intravenous infusion of either one of two doses of fentanyl (50 µg/70kg), naloxone (400 µg) or placebo (saline 0.9%), were included in the analyses. End tidal CO2 data were collected to control for respiratory depression.
Results: We demonstrated fentanyl induced increases in MID task reward and loss anticipation BOLD compared with placebo and naloxone in both region of interest (ROI) and whole brain analyses. These results were in cortical regions including the lingual gyrus, precuneus, posterior cingulate and frontal pole rather than the striatum.
Conclusions: Our results show the primary effects of fentanyl on MID anticipation BOLD in regions associated with the preparation of a motor response to a salient visual cue, rather than in regions typically associated with reward processing such as the striatum. This suggests that opioid agonists do not affect striatal activation during the MID task. Tasks using naturalistic rewards, for example feeding, sex or social contact which induce endogenous opioid signalling, may be more appropriate to probe the effects of fentanyl on reward processing. These results are from male participants' data and therefore may not be generalisable to female participants.
期刊介绍：
Official Journal of the European Behavioural Pharmacology Society (EBPS)
Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields:
Human Psychopharmacology: Experimental
This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered.
Human Psychopharmacology: Clinical and Translational
This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects.
Preclinical psychopharmacology: Behavioral and Neural
This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels.
Preclinical Psychopharmacology: Translational
This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways.
Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic
This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.
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