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DREAM ablation selectively alters THC place aversion and analgesia but leaves intact the motivational and analgesic effects of morphine
Author(s) -
Cheng HaiYing M.,
Laviolette Steven R.,
Van Der Kooy Derek,
Penninger Josef M.
Publication year - 2004
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.0953-816x.2004.03435.x
Subject(s) - dynorphin , morphine , dream , psychology , opioid , pharmacology , analgesic , (+) naloxone , neuroscience , receptor , medicine , opioid peptide
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 [Δ 9 ‐tetrahydrocannabinol (THC)] and cocaine in mice lacking the dream gene ( dream −/− ). The aversive effects of THC were potentiated in dream −/− mice in a κ‐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.