Neurobehavioral Differences of Valproate and Risperidone on MK-801 Inducing Acute Hyperlocomotion in Mice

Area of Science:

• Neuropharmacology
• Psychopharmacology
• Neuroscience

Background:

• The glutamate system is implicated in neuropsychiatric disorders like psychosis and addiction.
• MK-801 (dizocilpine), an NMDA receptor antagonist, induces schizophrenic-like behaviors in mice, including hyperactivity.
• Understanding drug effects on these behaviors is crucial for developing treatments.

Purpose of the Study:

• To investigate the neuropharmacological effects of risperidone and valproic acid on MK-801-induced behavioral changes.
• To compare the efficacy of risperidone and valproic acid in mitigating MK-801-induced hyperlocomotion and stereotyped behaviors.

Main Methods:

• Male C57BL/6J mice were used to assess drug effects on locomotor activity and gait.
• Mice received injections of risperidone (0.1 mg/kg) or valproic acid (200 mg/kg) followed by MK-801 (0.2 mg/kg).
• Locomotion, speed, step angles, stride lengths, and stance widths were measured using a video-tracking system.

Main Results:

• Neither risperidone nor valproic acid alone affected locomotor activity.
• MK-801 significantly increased locomotion and speed.
• Risperidone completely inhibited MK-801-induced hyperlocomotion, whereas valproic acid partially suppressed it.

Conclusions:

• Risperidone demonstrated a more potent effect in reversing MK-801-induced hyperlocomotion compared to valproic acid.
• The partial suppression by valproic acid suggests a potential adjuvant role in treating psychosis by modulating glutamatergic neurotransmission.