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The Journal of Neuroscience, December 1, 2001, 21(23):9499-9505

Absence of -9-Tetrahydrocannabinol Dysphoric Effects in Dynorphin-Deficient Mice

Andreas Zimmer^{1, 2}, Emmanuel Valjent³, Monika König¹, Anne M. Zimmer^{1, 2}, Patricia Robledo³, Heidi Hahn¹, Olga Valverde³, and Rafael Maldonado³

¹ Laboratory of Genetics, National Institute of Mental Health, Bethesda, Maryland 20892, ² Psychiatric Clinic, University of Bonn, 53105 Bonn, Germany, and ³ Laboratori de Neurofarmacologia, Facultat de Ciències de la Salut i de la Vida, Universitat Pompeu Fabra, 08003 Barcelona, Spain

The involvement of dynorphin on -9-tetrahydrocannabinol (THC) and morphine responses has been investigated by using mice with a targeted inactivation of the prodynorphin (Pdyn) gene. Dynorphin-deficient mice show specific changes in the behavioral effects of THC, including a reduction of spinal THC analgesia and the absence of THC-induced conditioned place aversion. In contrast, acute and chronic opioid effects were normal. The lack of negative motivational effects of THC in the absence of dynorphin demonstrates that this endogenous opioid peptide mediates the dysphoric effects of marijuana.

Key words: cannabinoid; opioid; mice; mutation; withdrawal; addiction; place aversion

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Copyright © 2001 Society for Neuroscience  0270-6474/01/21239499-07$05.00/0

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				P. Pacher, S. Batkai, and G. Kunos The Endocannabinoid System as an Emerging Target of Pharmacotherapy Pharmacol. Rev., September 1, 2006; 58(3): 389 - 462. [Abstract] [Full Text] [PDF]

				R. Maldonado and F. Rodriguez de Fonseca Cannabinoid Addiction: Behavioral Models and Neural Correlates J. Neurosci., May 1, 2002; 22(9): 3326 - 3331. [Abstract] [Full Text] [PDF]

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