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Role of μ-opioid system in the formation of memory of placebo responses

Molecular Psychiatry volume 18, pages 135–137 (2013)Cite this article

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Learning motivated behaviors seem critical for the development1 and presumably, sustainability of placebo responses. However, the neurobiology of long-term forms of placebo responses in humans is largely unexplored. A body of literature has implicated dopaminergic neurotransmission in both, placebo responses2, 3 and learning motivated behaviors.4 However, the contribution of other placebo-related neurotransmitter systems, such as the endogenous opioid, to learning in a motivational context, has not been studied in humans. In vitro studies on neurons in the hippocampus have shown that μ-opioid receptor agonists facilitate long-term potentiation by increasing the excitability of hippocampal pyramidal and dentate granule cells,5 and enkephalins have been involved in the attenuation of amnesia.6

A network of regions including the rostral anterior cingulate, dorsolateral prefrontal and orbitofrontal cortices, insula, ventral striatum, amygdala, medial thalamus and periaqueductal gray are involved in acute placebo analgesia.2 These brain areas partly overlap and demonstrate substantial connectivity with traditional memory and cognitive circuits such as the cortico-limbic pathway, the Papez circuit or the septo-hippocampal pathway,7 where high concentrations of μ-opioid receptors have also been described.8

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References

  1. Colloca L, Miller FG . Philos Trans R Soc Lond B Biol Sci 2011; 366: 1859–1869.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Scott DJ, Stohler CS, Egnatuk CM, Wang H, Koeppe RA, Zubieta JK . Arch Gen Psychiatry 2008; 65: 220–231.

    Article  PubMed  Google Scholar 

  3. de la Fuente-Fernandez R . Parkinsonism Relat Disord 2009; 15 (Suppl 3): S72–S74.

    Article  PubMed  Google Scholar 

  4. Adcock RA, Thangavel A, Whitfield-Gabrieli S, Knutson B, Gabrieli JD . Neuron 2006; 50: 507–517.

    Article  CAS  PubMed  Google Scholar 

  5. Simmons ML, Chavkin C . Int Rev Neurobiol 1996; 39: 145–196.

    Article  CAS  PubMed  Google Scholar 

  6. Rigter H . Science 1978; 200: 83–85.

    Article  CAS  PubMed  Google Scholar 

  7. Liu MG, Chen J . Neurosci Bull 2009; 25: 237–266.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Arvidsson U, Riedl M, Chakrabarti S, Lee JH, Nakano AH, Dado RJ et al. J Neurosci 1995; 15 (5 Part 1): 3328–3341.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Bostock E, Gallagher M, King RA . Behav Neurosci 1988; 102: 643–652.

    Article  CAS  PubMed  Google Scholar 

  10. Alreja M, Shanabrough M, Liu W, Leranth C . J Neurosci 2000; 20: 1179–1189.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA

    M Peciña & J-K Zubieta

  2. School of Dentistry, University of Maryland, Baltimore, MD, USA

    C S Stohler

  3. Departments of Psychiatry and Radiology, Medical School, University of Michigan, Ann Arbor, MI, USA

    J-K Zubieta

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  1. M Peciña
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  2. C S Stohler
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  3. J-K Zubieta
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Correspondence to J-K Zubieta.

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Peciña, M., Stohler, C. & Zubieta, JK. Role of μ-opioid system in the formation of memory of placebo responses. Mol Psychiatry 18, 135–137 (2013). https://doi.org/10.1038/mp.2012.16

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