Synergistic effect between D-AP5 and muscimol in the nucleus accumbens shell on memory consolidation deficit in adult male Wistar rats: An isobologram analysis

Abstract

The nucleus accumbens (NAc) glutamatergic and GABAergic systems are involved in memory processes. This study was investigated the involvement of NAc shell GABAergic system on D-AP5 induced memory consolidation deficit. The elevated plus-maze (EPM) test-retest paradigm was employed to assess memory in adult male Wistar rats. The results indicated that post-training intra-NAc shell injection of bicuculline (GABA receptor antagonist) did not alter emotional memory consolidation. However, post-training intra-NAc shell microinjection of muscimol (GABA receptor agonist, 0.1μg/rat) and D-AP5 (a competitive NMDA receptor antagonist, 4μg/rat) decreased emotional memory consolidation, suggesting the drugs induced amnesia. Moreover, a sub-threshold dose of muscimol (0.05μg/rat) potentiated the D-AP5 (2μg/rat) response on memory consolidation impairment. On the other hand, the middle dose of bicuculline (0.25μg/rat) reversed memory impairment induced by D-AP5 at the higher dose. Interestingly, there is a synergistic effect between D-AP5 and muscimol on impairment of emotional memory consolidation. None of the above doses changed the locomotor activity. Our results suggest that the glutamatergic and GABAergic neurons of the NAc shell interact with each other for modulation of emotional memory consolidation.

Synergistic antidepressant- and anxiolytic-like effects of harmaline along with cinanserin in acute restraint stress-treated mice

“…When the experimental ED50 was significantly lower than the theoretical ED50, a synergistic interaction between harmaline and cinanserin could be concluded. Nonetheless, there was not any difference between them presenting additive interaction rather than the synergistic effect (Nasehi et al 2016(Nasehi et al , 2017bNejati et al 2020). Differences with P < 0.05 between the experimental groups at each point were exhibited statistically significant.…”

“…Furthermore, isobolographic analysis was done to identify the interactions following the administration of the two drugs (Nasehi et al 2016(Nasehi et al , 2017bNejati et al 2020). The ED50 of each drug (0.31 mg/kg for harmaline and 2.5 μg/mouse for cinanserin) was analyzed by linear regression analysis and a combination of the two drugs was administrated in a constant dose ratio based on the ED50 values.…”

“…To confirm whether harmaline and cinanserin coadministration would exert additive or synergistic effects on their induced effects, the isobolographic analysis was done to compare the theoretical and experimental ED50 of the drugs when administrated together. According to the dose-response curve of harmaline and cinanserin, mice of ARS received harmaline 0.31 mg/kg + cinanserin 2.5 μg/mouse, harmaline 0.155 mg/kg + cinanserin 1.25 μg/mouse, and harmaline 0.077 mg/kg + cinanserin 0.625 μg/mouse (Nasehi et al 2016;Nasehi et al 2017b;Nejati et al 2020).…”

GABA‐ergic agents modulated the effects of histamine on the behaviour of male mice in the elevated plus maze test

“…Additionally, an isobolographic analysis was used to recognize the interactions following the injection of the two drugs (Nasehi et al, 2016b(Nasehi et al, , 2017Nejati et al, 2020). The ED 50 of each drug test.…”

“…Additionally, an isobolographic analysis was used to recognize the interactions following the injection of the two drugs (Nasehi et al., 2016b, 2017; Nejati et al., 2020). The ED 50 of each drug (1.25 μg/mouse for histamine and 0.25 mg/kg for bicuculline) was analysed by linear regression and a combination of the two drugs was injected in a constant dose ratio based on the ED 50 values.…”