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Research Articles, Behavioral/Cognitive

Vaporized Cannabis Extracts Have Reinforcing Properties and Support Conditioned Drug-Seeking Behavior in Rats

Timothy G. Freels, Lydia N. Baxter-Potter, Janelle M. Lugo, Nicholas C. Glodosky, Hayden R. Wright, Samantha L. Baglot, Gavin N. Petrie, Zhihao Yu, Brian H. Clowers, Carrie Cuttler, Rita A. Fuchs, Matthew N. Hill and Ryan J. McLaughlin
Journal of Neuroscience 26 February 2020, 40 (9) 1897-1908; DOI: https://doi.org/10.1523/JNEUROSCI.2416-19.2020
Timothy G. Freels
1Departments of Integrative Physiology and Neuroscience,
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Lydia N. Baxter-Potter
1Departments of Integrative Physiology and Neuroscience,
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Janelle M. Lugo
1Departments of Integrative Physiology and Neuroscience,
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Nicholas C. Glodosky
2Psychology,
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Hayden R. Wright
1Departments of Integrative Physiology and Neuroscience,
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Samantha L. Baglot
4Departments of Cell Biology and Anatomy and Psychiatry, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada
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Gavin N. Petrie
4Departments of Cell Biology and Anatomy and Psychiatry, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada
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Zhihao Yu
3Chemistry, Washington State University, Pullman, Washington 99164, and
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Brian H. Clowers
3Chemistry, Washington State University, Pullman, Washington 99164, and
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Carrie Cuttler
2Psychology,
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Rita A. Fuchs
1Departments of Integrative Physiology and Neuroscience,
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Matthew N. Hill
4Departments of Cell Biology and Anatomy and Psychiatry, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada
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Ryan J. McLaughlin
1Departments of Integrative Physiology and Neuroscience,
2Psychology,
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Article Information

DOI 
https://doi.org/10.1523/JNEUROSCI.2416-19.2020
PubMed 
31953372
Published By 
Society for Neuroscience
History 
  • Received October 9, 2019
  • Revision received January 3, 2020
  • Accepted January 8, 2020
  • First published January 17, 2020.
  • Version of record published February 26, 2020.
Copyright & Usage 
Copyright © 2020 the authors

Author Information

  1. Timothy G. Freels1,
  2. Lydia N. Baxter-Potter1,
  3. Janelle M. Lugo1,
  4. Nicholas C. Glodosky2,
  5. Hayden R. Wright1,
  6. Samantha L. Baglot4,
  7. Gavin N. Petrie4,
  8. Zhihao Yu3,
  9. Brian H. Clowers3,
  10. Carrie Cuttler2,
  11. Rita A. Fuchs1,
  12. Matthew N. Hill4, and
  13. Ryan J. McLaughlin1,2
  1. 1Departments of Integrative Physiology and Neuroscience,
  2. 2Psychology,
  3. 3Chemistry, Washington State University, Pullman, Washington 99164, and
  4. 4Departments of Cell Biology and Anatomy and Psychiatry, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada
View Full Text

Author contributions

  1. Author contributions: C.C., R.A.F., and R.J.M. designed research; T.G.F., L.N.B.-P., J.M.L., N.C.G., H.R.W., S.L.B., G.N.P., Z.Y., B.H.C., and M.N.H. performed research; T.G.F., L.N.B.-P., N.C.G., C.C., R.A.F., and R.J.M. analyzed data; B.H.C. and M.N.H. contributed unpublished reagents/analytic tools; R.J.M. wrote the paper.

Disclosures

    • Received October 9, 2019.
    • Revision received January 3, 2020.
    • Accepted January 8, 2020.
  • This work was supported by NIH NIDA Grants R21 DA043722-01A1 (R.J.M.) and R01 DA025646-07 (R.A.F.), by a Foundation Grant from the Canadian Institutes of Health Research to M.N.H., and with funding for medical and biological research by the State of Washington Initiative Measure No. 171 (R.J.M.). We thank Maury Cole for technical support and the Southern Alberta Mass Spectrometry Centre, located in and supported by the Cumming School of Medicine, University of Calgary, for their services in targeted liquid chromatography tandem mass spectrometry.

  • The authors declare no competing financial interests.

  • Correspondence should be addressed to Ryan J. McLaughlin at ryan.mclaughlin{at}wsu.edu

Other Version

  • previous version (January 17, 2020).
  • You are viewing the most recent version of this article.

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Jan 202025600125
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May 20202844017
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The Journal of Neuroscience: 40 (9)
Journal of Neuroscience
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26 Feb 2020
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Vaporized Cannabis Extracts Have Reinforcing Properties and Support Conditioned Drug-Seeking Behavior in Rats
Timothy G. Freels, Lydia N. Baxter-Potter, Janelle M. Lugo, Nicholas C. Glodosky, Hayden R. Wright, Samantha L. Baglot, Gavin N. Petrie, Zhihao Yu, Brian H. Clowers, Carrie Cuttler, Rita A. Fuchs, Matthew N. Hill, Ryan J. McLaughlin
Journal of Neuroscience 26 February 2020, 40 (9) 1897-1908; DOI: 10.1523/JNEUROSCI.2416-19.2020

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Vaporized Cannabis Extracts Have Reinforcing Properties and Support Conditioned Drug-Seeking Behavior in Rats
Timothy G. Freels, Lydia N. Baxter-Potter, Janelle M. Lugo, Nicholas C. Glodosky, Hayden R. Wright, Samantha L. Baglot, Gavin N. Petrie, Zhihao Yu, Brian H. Clowers, Carrie Cuttler, Rita A. Fuchs, Matthew N. Hill, Ryan J. McLaughlin
Journal of Neuroscience 26 February 2020, 40 (9) 1897-1908; DOI: 10.1523/JNEUROSCI.2416-19.2020
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Keywords

  • cannabinoid
  • cannabis
  • rat
  • self-administration
  • translational
  • vapor

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  • Habitual behaviors and addiction
    Jeff D Correa
    Published on: 08 February 2021
  • Published on: (8 February 2021)
    Page navigation anchor for Habitual behaviors and addiction
    Habitual behaviors and addiction
    • Jeff D Correa, Masters Student, Research Assistant, Carleton University

    This paper creates a good foundation in introducing the effects of vaporized cannabis on reinforcing drug-seeking behaviours. The authors focus on the motivational component of reward-oriented behaviours to habitual drug-seeking behaviours. The study introduces different fixed ratios to determine the effects of motivation, and their results demonstrate that effort influences increased self-administration of illicit drugs. However, motivation is only one aspect of this transition. Therefore, future studies should investigate the genomic changes, the second aspect of the transition from reward-oriented behaviours to habitual drug-seeking behaviours.

    Investigating the effects of THC exposure on the genes Cnr1, Grin1, Gin2a, and Gria2 of the dorsal striatum will help consolidate the transition from reward-oriented behaviours to habitual drug-seeking behaviours. These mRNA levels, if affected by THC administration, will demonstrate the progression from recreational drug use to addiction disorder [4].

    The Cnr1 gene encodes for the CB1 receptor, a direct target of THC, and is critical to forming striatal long-term depression (LTD) and synaptic plasticity [1] [2] [4]. The activity of the medium spiny neurons in the striatum regulates glutamatergic inputs and LTD [3]. Striatal LTD is closely associated with habitual behaviours and reinforcement learning [4] [5] [6]. With the investigation of Cnr1 and NMDA receptors in the striatum, you will be able to consolidate you...

    Show More

    This paper creates a good foundation in introducing the effects of vaporized cannabis on reinforcing drug-seeking behaviours. The authors focus on the motivational component of reward-oriented behaviours to habitual drug-seeking behaviours. The study introduces different fixed ratios to determine the effects of motivation, and their results demonstrate that effort influences increased self-administration of illicit drugs. However, motivation is only one aspect of this transition. Therefore, future studies should investigate the genomic changes, the second aspect of the transition from reward-oriented behaviours to habitual drug-seeking behaviours.

    Investigating the effects of THC exposure on the genes Cnr1, Grin1, Gin2a, and Gria2 of the dorsal striatum will help consolidate the transition from reward-oriented behaviours to habitual drug-seeking behaviours. These mRNA levels, if affected by THC administration, will demonstrate the progression from recreational drug use to addiction disorder [4].

    The Cnr1 gene encodes for the CB1 receptor, a direct target of THC, and is critical to forming striatal long-term depression (LTD) and synaptic plasticity [1] [2] [4]. The activity of the medium spiny neurons in the striatum regulates glutamatergic inputs and LTD [3]. Striatal LTD is closely associated with habitual behaviours and reinforcement learning [4] [5] [6]. With the investigation of Cnr1 and NMDA receptors in the striatum, you will be able to consolidate your findings and determine that THC affects the transition from reward-oriented to habitual compulsive drug-taking.

    Reference
    [1] Gerdeman GL, Ronesi J, Lovinger DM (2002). Postsynaptic endocannabinoid release is critical to long-term depression in the striatum. Nat Neurosci, 5, 446–451. doi:10.1038/nn832
    [2] Gerdeman GL, Partridge JG, Lupica CR, Lovinger DM (2003). It could be habit forming: drugs of abuse and striatal synaptic plasticity. Trends in neurosciences, 26, 184–192. doi: 10.1016/S0166-2236(03)00065-1
    [3] Grueter, B., Rothwell, P. and Malenka, R. (2012). Integrating synaptic plasticity and striatal circuit function in addiction. Current Opinion in Neurobiology, 22(3), 545-551. doi: 10.1016/j.conb.2011.09.009
    [4] Szutorisz, H., Dinieri, J. A., Sweet, E., Egervari, G., Michaelides, M., Carter, J. M., . . . Hurd, Y. L. (2014). Parental THC Exposure Leads to Compulsive Heroin-Seeking and Altered Striatal Synaptic Plasticity in the Subsequent Generation. Neuropsychopharmacology, 39(6), 1315-1323. doi: 10.1038/npp.2013.352
    [5] Szutorisz, H., Egervári, G., Sperry, J., Carter, J. and Hurd, Y. (2016). Cross-generational THC exposure alters the developmental sensitivity of ventral and dorsal striatal gene expression in male and female offspring. Neurotoxicology and Teratology, 58, 107-114. doi: 10.1016/j.ntt.2016.05.005
    [6] Yager, L., Garcia, A., Wunsch, A., & Ferguson, S. (2015). The ins and outs of the striatum: Role in drug addiction. Neuroscience, 301, 529-541. doi: 10.1016/j.neuroscience.2015.06.033

    Show Less
    Competing Interests: None declared.

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