Absence of delta -9-tetrahydrocannabinol dysphoric effects in dynorphin-deficient mice.
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.
Zimmer
A
A
Laboratory of Genetics, National Institute of Mental Health, Bethesda, Maryland 20892, USA.
Valjent
E
E
Konig
M
M
Zimmer
A M
AM
Robledo
P
P
Hahn
H
H
Valverde
O
O
Maldonado
R
R
D000698:Analgesia; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry; D013759:Dronabinol / Q000494:pharmacology*; D004399:Dynorphins / Q000032:analysis / Q000172:deficiency* / Q000235:genetics; D004745:Enkephalins / Q000172:deficiency / Q000235:genetics; D005260:Female; D018390:Gene Targeting; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009020:Morphine / Q000494:pharmacology; D009042:Motivation; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009294:Narcotics / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D011498:Protein Precursors / Q000172:deficiency / Q000235:genetics; D017473:Receptors, Opioid, kappa / Q000172:deficiency / Q000187:drug effects / Q000235:genetics; D013037:Spatial Behavior / Q000187:drug effects; D019966:Substance-Related Disorders / Q000503:physiopathology*
D000701:Analgesics, Opioid; D004745:Enkephalins; D009294:Narcotics; D011498:Protein Precursors; D017473:Receptors, Opioid, kappa; D004399:Dynorphins; D009020:Morphine; D013759:Dronabinol; C033660:preproenkephalin