Related Experiment Video
Updated: Jun 4, 2026
Developing a Rat Model for Bipolar Disorder
Published on: May 2, 2025
Memantine reduces mania-like symptoms in animal models
Yonglin Gao1, Ralphiel S Payne, Avital Schurr
1Mood Disorders Research Program, Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine, Louisville, KY 40202, United States.
Abstract:
Memantine, a selective antagonist of the N-methyl-D-aspartate receptor, is approved for the treatment of moderate to severe Alzheimer's disease. Ion dysregulation is thought to be involved in the pathophysiology of bipolar illness, suggesting that memantine may be effective in treating bipolar manic and/or depressive episodes. We utilized two preclinical models of mania that mimic pathophysiologic changes seen in bipolar illness to examine the potential efficacy of memantine in the treatment of this disorder. Locomotor hyperactivity of male Sprague-Dawley rats in an open field was induced with intracerebroventricular (ICV) administration of 10(-3) M ouabain. Memantine (2.5, 5 or 7.5mg/kg), lithium (6.75 mEq/kg), or vehicle were administered acutely via intraperitoneal injection immediately prior to ouabain, then chronically for 7 days (oral memantine 20, 30, and 40 mg/kg/day in water; lithium 2.4 g/kg food). In a second model of bipolar disorder, cycling between population spikes and epileptiform bursts was investigated in rat hippocampal slices treated with ouabain (3.3 μM) alone or in combination with memantine (0.5, 1.0, and 5.0 μM). Ouabain-induced hyperlocomotion was normalized with acute and chronic lithium and chronic use of memantine. Memantine delayed the onset of ouabain-induced-cycling in hippocampal slices. Memantine may have antimanic properties.
Insights
Memantine, an N-methyl-D-aspartate receptor antagonist, demonstrated antimanic properties in preclinical models. Chronic memantine treatment normalized hyperactivity and delayed epileptiform bursts, suggesting potential for bipolar disorder treatment.
Area of Science:
- Neuroscience
- Pharmacology
- Psychiatry
Background:
- Ion dysregulation is implicated in bipolar disorder pathophysiology.
- Memantine, an N-methyl-D-aspartate receptor antagonist, is approved for Alzheimer's disease.
- Preclinical models can investigate potential treatments for bipolar disorder.
Purpose of the Study:
- To evaluate the efficacy of memantine in preclinical models of mania and bipolar disorder.
- To assess memantine's effects on ouabain-induced hyperactivity and epileptiform activity.
- To compare memantine's effects with lithium, a known mood stabilizer.
Main Methods:
- Two rat models were used: ouabain-induced locomotor hyperactivity and ouabain-treated hippocampal slices.
- Animals received acute or chronic administration of memantine, lithium, or vehicle.
- Electrophysiological recordings assessed synaptic activity in hippocampal slices.
Main Results:
- Chronic memantine administration normalized ouabain-induced hyperlocomotion in rats.
- Memantine treatment delayed the onset of ouabain-induced cycling in hippocampal slices.
- Both acute and chronic lithium also normalized hyperactivity, serving as a positive control.
Conclusions:
- Memantine exhibits potential antimanic properties.
- The N-methyl-D-aspartate receptor antagonist may be a viable therapeutic option for bipolar disorder.
- Further research is warranted to explore memantine's efficacy in human clinical trials for bipolar disorder.
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