The Balb/c mouse strain is more sensitive than other strains to MK-801, a drug that blocks NMDA receptors, showing a higher threshold for seizures and irregular jumping behavior. This sensitivity suggests Balb/c mice may model psychosis-proneness. The study compared protein expression of NMDA receptor subunits in the hippocampus and cerebral cortex of Balb/c and NIH Swiss mice but found that differences in these subunits do not explain the behavioral differences.
A reduced level of the alpha7-nicotinic acetylcholine receptor in certain brain areas may contribute to sensory and movement deficits in schizophrenia and might be a necessary condition for the disorder. This has led to interest in drugs that activate this receptor. In a mouse model, the drug anabasine, a selective alpha7-nicotinic receptor agonist, reduced popping behavior caused by MK-801 (a drug that mimics schizophrenia-like symptoms) at a dose that did not cause seizures. The findings suggest potential therapeutic benefit for schizophrenia, but also highlight the need to consider seizure risk.
The NMDA receptor antagonist MK-801 (dizocilpine) induces intense, irregular jumping behavior (popping) in mice, modeling NMDA receptor hypofunction implicated in schizophrenia. Galantamine, which enhances nicotinic neurotransmission through acetylcholinesterase inhibition and positive allosteric modulation, significantly reduced MK-801-elicited popping at a dose of 100 mg/kg. This demonstrates that nicotinic interventions can influence NMDA receptor-mediated neurotransmission in mice, supporting the potential of nicotinic modulation as a therapeutic strategy for schizophrenia.