Memory Loss May Be Reversed With New Treatment Developed At Yale

New Haven, Conn. -- Working memory loss can be reversed using a short-term drug regimen that produces long-lasting effects, a Yale study has found.

Results from this study led by Stacy Castner at Yale School of Medicine may ultimately lead to new treatment strategies for those who have lost working or short-term memory. The team's past studies suggest that long-term treatment with antipsychotic medications for diseases such as schizophrenia, decrease the number of D1 receptors in cortical neurons. D1 receptors are one of five known dopamine receptors, which control memory function.

Published in the March 17 issue of Science, results from this new study show that long-term treatment with antipsychotic drugs produces memory impairments when the treatment lasts over several months.

"We also found that the memory deficits produced by anti-psychotic drugs can be reversed by stimulating D1 receptors with a D1 agonist-a drug that stimulates mainly D1 receptors," said Castner, associate research scientist at Yale School of Medicine.

The D1 agonist used in the study was ABT-431, an experimental and not yet available drug which effectively reversed memory loss in six primates. The improvements have been sustained for more than a year.

The return of short-term memory, which is often lost due to age and diseases such as schizophrenia and Parkinson's, is critical because short-term memory allows individuals to briefly hold information in mind while the knowledge is processed to determine an appropriate action.

It only took a relatively short treatment regimen of 25 days to get a positive effect, and it could be even shorter with the same effect, said Castner. The improvement in memory persisted for months and years after the last treatment, suggesting that the state of the circuitry involved in memory processing had been permanently or semi-permanently restored to a different level of sensitivity.

Castner's team included Patricia Goldman-Rakic and Graham V. Williams in the section of neurobiology at Yale School of Medicine. The research was supported by Hoechst Marion Rousell (now Aventis Pharmaceuticals); the National Institute of Mental Health; and the National Institute on Drug Abuse.