Intracellular mechanisms and behavioral changes in mouse model of attention deficit hyperactivity disorder: Importance of age-specific NMDA receptor blockade

Publication date: Available online 20 November 2019Source: Pharmacology Biochemistry and BehaviorAuthor(s): Harish M. Kawade, Chandrashekhar D. Borkar, Ashwini S. Shambharkar, Omprakash Singh, Praful S. Singru, Nishikant K. Subhedar, Dadasaheb M. KokareAbstractExposure of NMDA receptor antagonists during developmental stages leads to behavioral consequences like attention deficit hyperactivity disorder (ADHD). However, the underlying molecular mechanisms have remained poorly understood. Herein, we studied the phosphorylated Akt (pAkt) and caspase-3, the key regulators of neuronal cell survival/death, as the probable downstream targets of MK-801 often used to engender ADHD-like condition. Swiss albino mice at postnatal days (PND) 7, 14 or 21 were injected with a single dose of MK-801 and evaluated for hyperactivity (open field test) and memory deficit at adolescence (PND 30) and adult stages (PND 60). PND 7 or 14 treatment groups (but not PND 21) consistently showed hyperactivity at the adolescence stage. A significant increase in working and reference memory errors in radial arm maze was noted at the adolescence age. PND 7 group continued to display the symptoms even in adulthood. All the treatment groups showed a significant decrease in the percent alterations (Y-maze) and discrimination index (novel object recognition test) at adolescence age. A significant increase in caspase-3 expression was noted in the prefrontal cortex (PFC) and hippocampus, whereas increased pAkt was ...
Source: Pharmacology Biochemistry and Behavior - Category: Biochemistry Source Type: research