Smoking Could Help Treat Schizophrenia
Among the variety of symptoms of schizophrenia are cognitive deficits, including disrupted memory and attention. Nicotine has been shown to improve these areas in schizophrenia sufferers. How this occurs is not fully established, although a team of scientists in Germany have proposed an explanation. To do this, they generated a ‘schizophrenic’ mouse line. These mice overexpress a single gene shown to be involved in cases of the disease. While this doesn’t come close to providing a full account of the complexity of schizophrenia, these mice did show deficits in the same cognitive areas as human schizophrenics. The next step was to provide a continuous stream of nicotine at levels similar to those found in smokers and then to observe the effects.
As expected, the control mice did not benefit from the nicotine – with disruption to cognitive performance. In the ‘schizophrenic’ mice, nicotine was effective at restoring impaired prepulse inhibition – the ability to filter out irrelevant stimuli – working memory – ultra short-term memory used for tasks (such as remembering where you just put your keys) – and social recognition. So nicotine was providing some relief from these symptoms, providing evidence for the self-medication hypothesis.
Going further, the research team wanted to see how exactly nicotine might be helping on a molecular level. Since nicotine acts on particular types of receptor, these were the clear targets of their investigation. In the brain the two most common nicotine receptors are known as alpha-4-beta-2 and alpha-7. The first subtype is thought to play a key role in nicotine addiction and the second subtype in cognition and memory. While chronic nicotine in these ‘schizophrenic’ mice did not seem to have an effect on alpha-4-beta-2 receptors compared to controls, alpha-7 receptors were increased in the hippocampus of these mice. Perhaps this observed increase is the reason behind why nicotine helps cognition in people with schizophrenia.
Hambsch B, Keyworth H, Lind J, Otte DM, Racz I, Kitchen I, Bailey A, Zimmer A. Chronic nicotine improves short-term memory selectively in a G72 mouse model of schizophrenia. British Journal of Pharmacology, 2014; 171 (7): 1758-1771