Antagonization of monoamine reuptake transporters by agmatine improves anxiolytic and locomotive behaviors commensurate with fluoxetine and methylphenidate

Background Agmatine (AGM) is known for its protective effects including neuroprotection, nephroprotection, gastroprotection, cardioprotection, and glucoprotection. Studies have validated the neuroprotective role of AGM as antidepressant, anxiolytic, locomotive, and antipsychotic agent in psychopathologies. Fluoxetine (FLX) is the most extensively prescribed antidepressant while methylphenidate (MPD) is the most frequently prescribed psychoactive stimulant for ADHD (attention deficit hyperactivity disorder) treatment worldwide. The mechanism of action of FLX and MPD involves reuptake inhibition of serotonin and dopamine and norepinephrine at presynaptic transporters. Present study was designed to determine the safety and efficacy of AGM administration along with conventional antidepressant and psychostimulative drugs. The study also aimed to establish underlying mechanism of action of AGM at monoamine reuptake transporters. Results AGM significantly ameliorated locomotion in activity box and open field while anxiolytic behaviors in light/dark transition box and EPM were also improved (p<0.01). The growth and appetite of animals were enhanced along with antidepressive behavior in FST (p<0.01). Moreover, co-administration of AGM with FLX or MPD improved rats’ behaviors as compared to single AGM administration. Conclusion Present study determined the significant anxiolytic, locomotor, and antidepressive effects of AGM compared with FLX and MPD. The study also showed improved behaviors of rats treated with combined doses of AGM with FLX or MPD along with food intake and body weights. This study has also proposed the potential mechanism of action of AGM at monoamine receptors that may lead to inhibition of monoamine reuptake transporters that may lead to increase in 5-HT, D, and NE concentrations at synaptic level.