Background: Diabetes mellitus (Type-2) patients display drastically elevated hyperarousal-related clinical conditions such as fear, panic, nervousness, pain, and seizures. Consequently, hyperarousal patients with inadequate metabolic outcomes (hyperglycemic condition) are usually treated with drugs affecting sodium / calcium channels, increasing the inhibitory (GABA) neurotransmission, and decreasing the excitatory (glutamatergic) neurotransmission, which results in a “hypoarousal” condition. This perilous clinical pathological condition of hyperglycemia and hypoarousal can result in severe learning disability and cognitive impairment.

Aims: Unfortunately, there are very few studies that has investigated the synergistic effect of hypoarousal and hyperglycemia on cognition. Hence, in this study we investigated the in vivo effect of alloxan (pyrimidone, barbituric acid derivative) and phenytoin (hydantoin-barbiturate) on rodent cognition. Furthermore, we also established the in-silico properties of these compounds on the GABA-A & Insulin receptor, Sodium Channels and GLUT-4 transporter.

Results: Administration of alloxan and phenytoin induced severe learning and cognitive deficiency as seen by the behavioral studies (elevated plus maze, Y-maze, Hebb’s William maze, and passive avoidance test). Our preliminary results indicate that this may be a valid animal model to identify new/novel therapeutic medications to treat hyperglycemic and hypoarousal related learning and cognitive deficiency.