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ARTICLE, Behavioral/Systems

Motivational Effects of Cannabinoids Are Mediated by μ-Opioid and κ-Opioid Receptors

Sandy Ghozland, Hans W. D. Matthes, Frederic Simonin, Dominique Filliol, Brigitte L. Kieffer and Rafael Maldonado
Journal of Neuroscience 1 February 2002, 22 (3) 1146-1154; https://doi.org/10.1523/JNEUROSCI.22-03-01146.2002
Sandy Ghozland
1Laboratori de Neurofarmacologia, Facultat de Ciéncies de la Salut i de la Vida, Universitat Pompeu Fabra, 08003 Barcelona, Spain, and
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Hans W. D. Matthes
2Centre National de la Recherche Scientifique Unité Propre de Recherche 9050, Ecole Superieure de Biotechnologie de Strasbourg, 67400 Illkirch, France
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Frederic Simonin
2Centre National de la Recherche Scientifique Unité Propre de Recherche 9050, Ecole Superieure de Biotechnologie de Strasbourg, 67400 Illkirch, France
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Dominique Filliol
2Centre National de la Recherche Scientifique Unité Propre de Recherche 9050, Ecole Superieure de Biotechnologie de Strasbourg, 67400 Illkirch, France
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Brigitte L. Kieffer
2Centre National de la Recherche Scientifique Unité Propre de Recherche 9050, Ecole Superieure de Biotechnologie de Strasbourg, 67400 Illkirch, France
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Rafael Maldonado
1Laboratori de Neurofarmacologia, Facultat de Ciéncies de la Salut i de la Vida, Universitat Pompeu Fabra, 08003 Barcelona, Spain, and
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Abstract

Repeated THC administration produces motivational and somatic adaptive changes leading to dependence in rodents. To investigate the molecular basis for cannabinoid dependence and its possible relationship with the endogenous opioid system, we explored Δ9-tetrahydrocannabinol (THC) activity in mice lacking μ-, δ- or κ-opioid receptor genes. Acute THC-induced hypothermia, antinociception, and hypolocomotion remained unaffected in these mice, whereas THC tolerance and withdrawal were minimally modified in mutant animals. In contrast, profound phenotypic changes are observed in several place conditioning protocols that reveal both THC rewarding and aversive properties. Absence of μ receptors abolishes THC place preference. Deletion of κ receptors ablates THC place aversion and furthermore unmasks THC place preference. Thus, an opposing activity of μ- and κ-opioid receptors in modulating reward pathways forms the basis for the dual euphoric–dysphoric activity of THC.

  • Δ9-tetrahydrocannabinol
  • place preference
  • place aversion
  • knock-out
  • tolerance
  • dependence
  • reward
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The Journal of Neuroscience: 22 (3)
Journal of Neuroscience
Vol. 22, Issue 3
1 Feb 2002
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Motivational Effects of Cannabinoids Are Mediated by μ-Opioid and κ-Opioid Receptors
Sandy Ghozland, Hans W. D. Matthes, Frederic Simonin, Dominique Filliol, Brigitte L. Kieffer, Rafael Maldonado
Journal of Neuroscience 1 February 2002, 22 (3) 1146-1154; DOI: 10.1523/JNEUROSCI.22-03-01146.2002

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Motivational Effects of Cannabinoids Are Mediated by μ-Opioid and κ-Opioid Receptors
Sandy Ghozland, Hans W. D. Matthes, Frederic Simonin, Dominique Filliol, Brigitte L. Kieffer, Rafael Maldonado
Journal of Neuroscience 1 February 2002, 22 (3) 1146-1154; DOI: 10.1523/JNEUROSCI.22-03-01146.2002
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Keywords

  • Δ9-tetrahydrocannabinol
  • place preference
  • place aversion
  • knock-out
  • tolerance
  • dependence
  • reward

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