Anxiolytic-like effect of succinic acid: A possible GABAergic intervention

In the modern era, physical and mental stress lead to anxiety at an alarming rate. Therefore, searching for new lead compounds that deal with anxiety has a practical demand. Our study aimed to evaluate succinic acid's (SUC) possibility of managing anxiety through in vivo and in silico studies. For this, SUC (5, 10, and 15) mg/kg were administered orally (p.o.) to the adult male Swiss mice, followed by several studies like open field, swing, hole cross, and light-dark residence tests. The GABAergic agonist diazepam (DZP-2 mg/kg) and an antagonist such as caffeine (CAF-10 mg/kg) were also studied in combination with the SUC group. In contrast to the DZP group, SUC significantly (p < 0.0001) increased the amount of time that animals spent in the light, suggesting that it may have relaxing impacts on mice. Additionally, in silico studies were carried out to understand the interaction between SUC and GABAA (alpha 1, ss 2, and gamma 2) receptor subunits. Furthermore, pharmacokinetic and drug-like properties were examined by pkCSM and SwissADME online servers and found to be supportive of considering SUC as a potential drug candidate. Our experiment found that SUC-10 had an anxiolytic-like effect on the animals. SUC-10, when combined with DZP, produced more significant (p < 0.0001) anxiolytic effects than their individual groups, suggesting possible synergistic effects with this commonly used anxiolytic drug. SUC-10 also altered CAF-mediated effects in mice. An in silico study demonstrates that SUC has good interaction capacity with GABAA receptor subunits. Taken together, SUC-10 exerted anxiolytic-like effects in Swiss mice. It may act synergistically with DZP while acting antagonistically with CAF, possibly through GABAergic interaction pathways.