Additive effect of harmane and muscimol for memory consolidation impairment in inhibitory avoidance task

Abstract

In the current study, we examined the effect of bilateral intra-dorsal hippocampal (intra-CA1) microinjections of GABA receptor agents on amnesia induced by a β-carboline alkaloid, harmane in mice. We used a single-trial step-down passive avoidance task to assess memory retention and then, open-field test to assess locomotor activity. The results indicated that post-training intra-CA1 injections of bicuculline - a GABA receptor antagonist - had no significant effect, while muscimol (0.01 and 0.1μg/mouse) - a GABA receptor agonist - impaired memory consolidation. Post-training intra-peritoneal (i.p.) infusion of harmane (3 and 5mg/kg) decreased memory consolidation. Furthermore, post-training intra-CA1 administration of sub-threshold dose of bicuculline (0.001μg/mouse) restored, whereas muscimol (0.001μg/mouse) potentiated impairment of memory consolidation induced by harmane. The isobologram analysis revealed that there is an additive effect between harmane and muscimol on impairment of memory consolidation. Moreover, all above doses of drugs did not alter locomotor activity. These findings suggest that GABA receptors of the CA1 area, at least partly, play a role in modulating the effect of harmane on 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, 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.…”

“…To confirm whether histamine and bicuculline co‐administration would exert additive or synergistic effects on induced behaviours, an isobolographic analysis was performed to compare the theoretical and experimental effective dose 50 (ED 50 ) of the drugs when injected together. According to the dose–response curve of histamine and bicuculline, mice received histamine 1.25 μg/mouse + bicuculline 0.25 mg/kg, histamine 0.625 μg/mouse + bicuculline 0.125 mg/kg and histamine 0.312 μg/mouse + bicuculline 0.0625 mg/kg (Nasehi et al., 2016b, 2017; Nejati et al., 2020).…”