Behavioral features and disorganization of oscillatory activity in C57BL/6J mice after acute low dose MK-801
Keke Cui1,2, Zhipeng Yu1, Le Xu1
1Department of Pharmacology, Ningbo University School of Medicine, Ningbo, China.
Abstract:
Low dose acute administration of N-methyl-D-aspartate receptor (NMDAR) antagonist MK-801 is widely used to model cognition impairments associated with schizophrenia (CIAS) in rodents. However, due to no unified standards for animal strain, dose, route of drug delivery, and the duration of administration, how different doses of MK-801 influence behavior and fundamental frequency bands of the local field potential (LFP) in cortical and subcortical brain regions without consistent conclusions. The optimal dose of MK-801 as a valid cognition impairers to model CIAS in C57BL/6J mice remains unclear. The current study characterizes the behavior and neural oscillation alterations induced by different low doses of MK-801 in medial prefrontal cortex (mPFC) and hippocampus CA1 of C57BL/6J mice. The results reveal that mice treated with 0.1 and 0.3 mg/kg MK-801 demonstrate increased locomotion and diminished prepulse inhibition (PPI), while not when treated with 0.05 mg/kg MK-801. We also find that MK-801 dose as low as 0.05 mg/kg can significantly diminishes spontaneous alteration during the Y-maze test. Additionally, the oscillation power in delta, theta, alpha, gamma and HFO bands of the LFP in mPFC and CA1 was potentiated by different dose levels of MK-801 administration. The current findings revealed that the observed sensitivity against spontaneous alteration impairment and neural oscillation at 0.05 mg/kg MK-801 suggest that 0.05 mg/kg will produce changes in CIAS-relevant behavior without overt changes in locomotion and sensorimotor processing in C57BL/6J mice.
Insights
Low doses of MK-801 impact rodent behavior and brain activity. A 0.05 mg/kg dose impairs cognition without affecting locomotion, making it suitable for modeling schizophrenia-related cognitive deficits.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- N-methyl-D-aspartate receptor (NMDAR) antagonist MK-801 is used to model cognitive impairments associated with schizophrenia (CIAS) in rodents.
- Lack of standardized protocols for MK-801 administration leads to inconsistent findings regarding its effects on behavior and neural oscillations.
Purpose of the Study:
- To characterize the behavioral and neural oscillation alterations induced by different low doses of MK-801 in C57BL/6J mice.
- To determine the optimal dose of MK-801 for modeling CIAS in C57BL/6J mice.
Main Methods:
- Administration of varying low doses of MK-801 (0.05, 0.1, and 0.3 mg/kg) to C57BL/6J mice.
- Behavioral testing including locomotion, prepulse inhibition (PPI), and Y-maze spontaneous alteration.
- Local field potential (LFP) recording in the medial prefrontal cortex (mPFC) and hippocampus CA1 to analyze neural oscillations.
Main Results:
- Doses of 0.1 and 0.3 mg/kg MK-801 increased locomotion and decreased PPI.
- A dose of 0.05 mg/kg MK-801 significantly diminished Y-maze spontaneous alteration.
- MK-801 administration at all tested doses potentiated oscillation power across multiple frequency bands (delta, theta, alpha, gamma, HFO) in the mPFC and CA1.
Conclusions:
- A low dose of 0.05 mg/kg MK-801 induces cognitive deficits relevant to CIAS without overt changes in locomotion or sensorimotor processing in C57BL/6J mice.
- This dose represents a potentially optimal choice for modeling CIAS due to its specific effects on cognitive behavior and neural oscillations.
