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Pharmacol Biochem Behav. 2013 Jun;107:20-3. doi: 10.1016/j.pbb.2013.03.017. Epub 2013 Apr 9.

Effects of ketamine and LY341495 on the depressive-like behavior of repeated corticosterone-injected rats.

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Discovery Pharmacology Ι, Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co. Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan.


In the present study, to further validate repeated corticosterone (CORT)-treated rats as a treatment-resistant depression (TRD) model, we first examined the effect of ketamine, which is known to be effective for the treatment of TRD, on the depressive-like behavior of CORT-treated rats. In this model, ketamine significantly reduced the increased immobility time of CORT-treated rats during the forced swim test (FST), indicating that its efficacy against TRD could be detected using this model. We next examined the effect of LY341495, a group ΙΙ metabotropic glutamate (mGlu2/3) receptor antagonist, in this model to evaluate its potential for the alleviation of TRD. LY341495, similar to ketamine, attenuated the increased immobility time of CORT-treated rats during the FST. Therefore, these results suggest that mGlu2/3 receptor antagonists might be effective for patients with depression, including TRD.

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