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

- Post-training infusion of bicuculline did not alter but muscimol impaired memory.
- I.p. injection of harmane impaired memory consolidation.
- Bicuculline decreased, but muscimol increased amnesia induced by harmane.
- There is an additive effect among harmane and muscimol on impairment of memory.
- GABAergic system of the CA1 may modulate harmane-induced amnesia.

In the current study, we examined the effect of bilateral intra-dorsal hippocampal (intra-CA1) microinjections of GABAA 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 GABAA receptor antagonist - had no significant effect, while muscimol (0.01 and 0.1 μg/mouse) - a GABAA receptor agonist - impaired memory consolidation. Post-training intra-peritoneal (i.p.) infusion of harmane (3 and 5 mg/kg) decreased memory consolidation. Furthermore, post-training intra-CA1 administration of sub-threshold dose of bicuculline (0.001 μg/mouse) restored, whereas muscimol (0.001 μg/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 GABAA receptors of the CA1 area, at least partly, play a role in modulating the effect of harmane on memory consolidation.