Are the endocannabinoids responsible for schizophrenia, especially the negative symptoms? A preclinical approach.
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Accession number;02A0472892
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| Title;Are the endocannabinoids responsible for schizophrenia, especially the negative symptoms? A preclinical approach. |
| Author;
YAMAMOTO TSUNEYUKI
(Kyudai Daigakuin'yakugakukenkyuin Yakkokaisekigaku)
YAMAGUCHI TAKU
(Kyudai Daigakuin'yakugakukenkyuin Yakkokaisekigaku)
KUBOTA TAKASHI
(Kyudai Daigakuin'yakugakukenkyuin Yakkokaisekigaku)
NOBE SAYORI
(Kyudai Daigakuin'yakugakukenkyuin Yakkokaisekigaku)
WATANABE SHIGENORI
(Kyudai Daigakuin'yakugakukenkyuin Yakkokaisekigaku)
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Journal Title;Annual Report of the Pharmacopsychiatry Research Foundation
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Journal Code:Y0939A
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ISSN:0286-7591
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VOL.;NO.34;PAGE.179-184(2002)
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| Figure&Table&Reference;FIG.4, REF.15 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;Abnormal behaviors induced by marijuana and/or cannabinoids in animals at least partially resemble symptoms of schizophrenia. Furthermore, it has been recently reported that endogenous cannabinoid levels are elevated in the cerebrospinal fluid of schizophrenic patients. Based on these, we adopted a novel approach investigating endocannabinoids in the brain in a hope to elucidate pathogenesis of schizophrenia, especially that of negative symptoms. Repeated tetrahydrocannabinol(THC) administration impaired delayed-matching-to-sample performance in rats, which may be a useful animal model for amotivational syndrome in humans. THC dose-dependently decreased the lever-pressing behavior(FR5) in rats, and the decrease was antagonized by cyclooxygenase inhibitors(diclofenac, aspirin and indomethacin) and EP3 receptor antisense-oligodeoxynucleotide. Furthermore, prostaglandin E2 given i.c.v. significantly decreased lever pressings. Judging from these findings, it is concluded that these THC-induced impairments may be due to the activation of arachidonic acid cascade in the brain. In addition, our results could lead to the development of novel therapeutic agents for the treatment of schizophrenia including negative symptoms. (author abst.) |
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