Regular use of nicotine may normalize brain activity impairments linked with schizophrenia, according to a study using a mouse model, published online in Nature Medicine. The finding may explain why up to 90% of people with schizophrenia smoke—most of them heavily.
“Basically the nicotine is compensating for a genetically determined impairment,” said researcher Jerry Stitzel, PhD, of the University of Colorado Boulder. “No one has ever shown that before.”
Dr. Stitzel is part of an international research team that investigated whether a variant in the CHRNA5 gene, which is believed to increase schizophrenia risk, is associated with a reduction of neural firing in the brain’s prefrontal cortex, or hypofrontality. Researchers also examined whether nicotine could interrupt the effect.
In mice with the CHRNA5 gene variant, brain images confirmed hypofrontality, researchers reported. Behavioral tests further revealed that the mice shared key characteristics of people with schizophrenia, such as an inability to suppress a startle response and aversion to social interaction. The findings, they explained, suggest the CHRNA5 gene variant plays a role in schizophrenia by causing hypofrontality.
Nicotine, however, seemed to reverse hypofrontality. When researchers gave the mice daily nicotine, their sluggish brain activity improved within 2 days. Within a week, it was normal.
Researchers believe the nicotine corrected the impaired brain activity by acting on nicotinic receptors in regions important for healthy cognitive function.
Noting that hypofrontality is also linked with addiction, attention deficit hyperactivity disorder, bipolar disorder, and other psychiatric conditions, researchers believe the discovery could lead to new nonaddictive, nicotine-based medications.
“This defines a completely novel strategy for medication development,” said lead author Uwe Maskos, PhD, of Institut Pasteur, Paris, France.
Koukouli F, Rooy M, Tziotis D, et al. Nicotine reverses hypofrontality in animal models of addiction and schizophrenia. Nature Medicine. 2017 January 23;[Epub ahead of print].
Nicotine normalizes brain deficits key to schizophrenia [press release]. Boulder, CO: University of Colorado Boulder; January 23, 2017.