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Non-nociceptive roles of opioids in the CNS: opioids’ effects on neurogenesis, learning, memory and affect

Nature Reviews Neurosciencevolume 20pages518 (2019) | Download Citation


Mortality due to opioid use has grown to the point where, for the first time in history, opioid-related deaths exceed those caused by car accidents in many states in the United States. Changes in the prescribing of opioids for pain and the illicit use of fentanyl (and derivatives) have contributed to the current epidemic. Less known is the impact of opioids on hippocampal neurogenesis, the functional manipulation of which may improve the deleterious effects of opioid use. We provide new insights into how the dysregulation of neurogenesis by opioids can modify learning and affect, mood and emotions, processes that have been well accepted to motivate addictive behaviours.

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Funding from the National Institutes of Health DA031442 (P-Y.L. and C.K.), the National Natural Science Foundation of China 81701313 (C.X.) and the Shirley and Stefan Hatos Neuroscience Research Foundation DA005010 (C.J.E. and C.M.C.) is gratefully acknowledged.

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Nature Reviews Neuroscience thanks Z. Georgoussi and the other anonymous reviewers for their contribution to the peer review of this work.

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  1. Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, Shirley and Stefan Hatos Center for Neuropharmacology, University of California, Los Angeles, CA, USA

    • Cherkaouia Kibaly
    • , Catherine M. Cahill
    • , Christopher J. Evans
    •  & Ping-Yee Law
  2. State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China

    • Chi Xu


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C.K, C.X., C.M.C., C.J.E. and P-Y.L. researched data for the article and made substantial contributions to the discussion of content and to the writing, review and editing of the manuscript before submission.

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The authors declare no competing interests.

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Correspondence to Cherkaouia Kibaly.

Supplementary Information



A broad term used to designate all substances, natural (for example, morphine) and synthetic (for example, fentanyl), that bind to opioid receptors in the nervous system.


A major anatomical structure located in the medial temporal lobe of the mammalian brain that processes a unidirectional flow of information via a trisynaptic loop.


The process by which we integrate sensory information from our interaction with our environment for behavioural adaptation.


The record left by a learning process.


A broad range of feelings that people can experience, embodying both emotions and moods.


An intense feeling that is short term and is typically directed at a source, often with facial expressions and body language.


The natural alkaloid compounds found in the opium poppy plant Papaver somniferum.

Neurogenic brain regions

In the adult mammal, these include the subgranular zone of the dentate gyrus in the hippocampus and the subventricular zone–oflactorybulb system.


A less specific and less intense state of mind than emotion that is less likely to be provoked by a particular event but lasts longer.

G2/M phase

A period of protein synthesis and rapid cell growth (G2) transitioning into division (M).

Cell cycle

A series of consecutive phases — Gap 1 (G1) phase, DNA synthesis (S) phase, Gap 2 (G2) phase (growth) and mitosis or meiosis (M) phase — that lead to the duplication and division of genetic information into two daughter cells.


(BrdU). A synthetic analogue of thymidine and marker of proliferating cells.

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