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

• Published in: The Journal of neuroscience Vol. 21; no. 23; pp. 9499 - 9505
• Main Authors: Zimmer, Andreas, Valjent, Emmanuel, Konig, Monika, Zimmer, Anne M, Robledo, Patricia, Hahn, Heidi, Valverde, Olga, Maldonado, Rafael
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 01.12.2001; Society for Neuroscience
• Subjects: Addiction; Analgesia; Analgesics, Opioid - pharmacology; Animals; Avoidance Learning - drug effects; Behavior, Animal - drug effects; Brain Chemistry; Cannabinoid; Cannabinoides; Dronabinol - pharmacology; Dynorphins - analysis; Dynorphins - deficiency; Dynorphins - genetics; Efectes fisiològics; Enkephalins - deficiency; Enkephalins - genetics; Female; Gene Targeting; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Mutant Strains; Morphine - pharmacology; Motivation; Motor Activity - drug effects; Motor Activity - genetics; Mutation; Narcotics - pharmacology; Opioid; Pain Measurement - drug effects; Place aversion; Protein Precursors - deficiency; Protein Precursors - genetics; Receptors; Receptors, Opioid, kappa - deficiency; Receptors, Opioid, kappa - drug effects; Receptors, Opioid, kappa - genetics; Spatial Behavior - drug effects; Substance-Related Disorders - physiopathology; Withdrawal
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.21-23-09499.2001

The involvement of dynorphin on Delta-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.