Evenamide reverses schizophrenia-related dysfunction in a neurodevelopmental animal model

Area of Science:

• Neuroscience
• Pharmacology
• Psychiatry

Background:

• Schizophrenia presents positive, negative, and cognitive symptoms, with current treatments primarily targeting positive symptoms.
• Limbic hippocampus hyperexcitability is a critical pathological feature of schizophrenia, indicating a potential therapeutic target.
• Evenamide, a selective voltage-gated sodium channel blocker, reduces neuronal hyperexcitability.

Purpose of the Study:

• To investigate the effects of evenamide on hyperdopaminergic state, hippocampal hyperexcitability, social deficits, and recognition memory.
• To evaluate evenamide's therapeutic potential in the methylazoxymethanol acetate (MAM) rat model of schizophrenia.

Main Methods:

• Utilized the MAM neurodevelopmental model in Sprague-Dawley rats (male and female).
• Performed electrophysiological recordings in the ventral tegmental area (VTA) and ventral hippocampus (vHipp).
• Assessed social approach and novel object recognition behaviors.

Main Results:

• Evenamide normalized dopamine neuron activity in the VTA and reduced hippocampal hyperactivity in MAM rats.
• Systemic and local evenamide administration in the vHipp reversed hyperdopaminergic states.
• Evenamide improved recognition memory and normalized social deficits in male MAM rats.

Conclusions:

• Evenamide's efficacy stems from its ability to reduce ventral hippocampus hyperexcitability.
• Evenamide demonstrates potential as a novel therapeutic strategy for schizophrenia, addressing multiple symptom domains.
• This study highlights evenamide's capacity to target positive, cognitive, and negative symptoms of schizophrenia.