DREAM ablation selectively alters THC place aversion and analgesia but leaves intact the motivational and analgesic effects of morphine.
DREAM (downstream regulatory element antagonistic modulator) is a novel transcriptional repressor for the prodynorphin gene, and genetic deletion of DREAM in mice results in a phenotype of ongoing analgesia by virtue of its effect on opioid gene expression. In the present study, we evaluated the motivational effects of opioids (morphine), cannabinoids [Delta(9)-tetrahydrocannabinol (THC)] and cocaine in mice lacking the dream gene (dream(-/-)). The aversive effects of THC were potentiated in dream(-/-) mice in a kappa-opioid receptor-dependent fashion, whereas morphine reward and the aversive effects of morphine withdrawal remained intact. The rewarding and aversive effects of cocaine were likewise unperturbed in dream(-/-) mice. Moreover, the aversive properties of lithium chloride and naloxone were unaffected by the absence of DREAM, indicating that the effect of DREAM on THC-induced dysphoria is not due to a general involvement in the behavioral response to aversive stimuli. Additionally, physical dependence to morphine and the locomotor-sensitizing effects of cocaine were unaltered in these animals. Finally, whereas the absence of DREAM reduced the analgesic efficacy of THC, morphine analgesia was unaffected in dream(-/-) mice.
Cheng
Hai-Ying M
HY
Departments of Medical Biophysics and Immunology, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9. hymcheng@yahoo.ca
Laviolette
Steven R
SR
van der Kooy
Derek
D
Penninger
Josef M
JM
D000698:Analgesia; D000700:Analgesics / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal; D003042:Cocaine / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology*; D009042:Motivation; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
D000700:Analgesics; D009292:Narcotic Antagonists; D012097:Repressor Proteins; D014157:Transcription Factors; D009270:Naloxone; D009020:Morphine; D013759:Dronabinol; D018021:Lithium Chloride; D003042:Cocaine