Figure 4.

Effects of ZJ43 and (R,S)-2-phosphono-methylpentanedioic acid (2-PMPA) on dizocilpine (MK-801)-induced cognitive deficit in the novel object recognition test. C57BL mice were injected (INJ) with by MK-801 (0.2 mg kg⁻¹, intraperitoneally (i.p.)) or saline 20 min after i.p. injection with: (a) saline (s), ZJ43 (50, 100 or 150 mg kg⁻¹) or 150 mg kg⁻¹ ZJ43 with LY341495 (1 mg kg⁻¹); (b) 2-PMPA (10, 50, 100 mg kg⁻¹), 100 mg kg⁻¹ 2-PMPA with LY341495 (1 mg kg⁻¹), or LY341495 (1 mg kg⁻¹) and 30 min later placed in a chamber with two identical objects for a 10-min acquisition session (AS) 30 min. Mice were tested with one original and one novel object in a recognition session (RS) 90 min after the AS. The recognition index for the AS was calculated as: (time exploring one of the objects/ time exploring both the objects) × 100. For the RS, the recognition index was calculated as: (time exploring the novel object/ time exploring the familiar and the novel object) × 100. (a) Saline-treated mice attended the novel object about twice as much as the familiar object. MK801 given before the AS blocked memory of the familiar object during the RS. ZJ43 (100 and 150 mg kg⁻¹) blocked the effects of MK-801. The effect of ZJ43 (150 mg kg⁻¹) on MK-801 was reversed by 1 mg kg⁻¹ of the metabotropic glutamate receptor 2/3 antagonist LY341495. ZJ43 (100 mg kg⁻¹) was not effective in blocking the MK-801 effect when given immediately after the AS. n=9–24 mice per group. (b) 2-PMPA dose-response on MK-801-induced cognitive deficits in the novel object recognition test. 2-PMPA (100 and 150 mg kg⁻¹) blocked the effect of MK-801. LY341495 (1 mg kg⁻¹) blocked the effect of 2-PMPA (100 mg kg⁻¹) on MK-801. n=5–24 mice per group. Data for the saline (s-s) and saline+MK-801 (s MK) are the same as in a and b, respectively.