(Great Neck, N.Y. - June 15, 2009) — Levels of a substance called kynurenic acid (KYNA) are elevated in the brain and cerebrospinal fluid of people with schizophrenia and Alzheimer’s disease, and KYNA had been suspected of a role in the cognitive dysfunction characteristic of both these disorders.
Now, studies by NARSAD Investigator David Bucci, Ph.D., and colleagues in Dartmouth College’s department of psychological and brain sciences, have shown that elevated concentrations of endogenous KYNA interfere with contextual learning and memory. The findings were reported in the March 19 online edition of the journal Behavioural Brain Research.
In Dr. Bucci’s experiments, rats received injections of solutions of l-kynurenine (L-KYN), the precursor for KYNA. Administration of L-KYN has been shown to produce clinically relevant increases in KYNA concentration. The treated rats exhibited impaired contextual fear memory compared to control rats. In an experiment in which the rats were trained to discriminate between two different training environments, one in which foot shock was delivered and one that was not paired with foot shock, both groups eventually learned the discrimination, but learning was slower in L-KYN-treated rats.
KYNA acts on molecules called nicotinic acetylcholine receptors, the receptors affected by smoking. People with schizophrenia smoke much more than people in the general population, which has suggested that they use nicotine as a form of self-medication. Dr. Bucci and his team have shown that that acute nicotine administration in laboratory rats reduced their KYNA levels.
Dr. Bucci wrote: “It is interesting to consider the possibility that cigarette smoking may be used by those with schizophrenia to attenuate cognitive and sensory deficits. Future studies in rat models should examine the capacity for nicotine treatment to reduce the deficits produced by upregulation of brain KYNA.”
(This article was adapted with permission from Elsevier, publisher of Behavioural Brain Research.)
Link to article: http://www.narsad.org/news/press/rg_2009/res2009-06-15.html