Shape of Brain Cells Influences Sensitivity to Cocaine, Yale Researchers Report

The learning ability of mice and their sensitivity to cocaine are influenced by the shape of their brain cells, Yale University researchers report in the Sept. 7-13 issue of the journal of Proceedings of the National Academies of Science.

Researchers had previously shown that cocaine can affect the shape of brain cells in mice, but it was unknown whether the change in the structure of neurons influenced behavior.

They do, according to findings of the Yale team of Jane Taylor, professor of psychiatry, Anthony Koleske, a professor of molecular biophysics and biochemistry, and neurobiology and Shannon Gourley, a postdoctoral fellow in psychiatry.

Cell shape is thought to affect learning and memory processes because a neuron’s shape dictates its ability to make connections with other cells. Directly testing this hypothesis has been challenging due to difficulties in subtly changing a neuron’s shape. Cell shape in the frontal cortex, the brain region important for decision-making, does not stabilize until late adolescence. Prior to this period, adolescents are at increased risk of seeking and using drugs.

The team genetically modified adult mice so their brain cells were unable to stabilize as they would in late adolescence or early adulthood. As adults, these mice — like normal adolescent mice — showed heightened sensitivity to the pleasurable effects of cocaine when compared to normal adult mice.

The team also assessed the performance of these mice in a behavioral test in which they could win food rewards by keeping track of instructive cues. To earn food pellets, mice had to follow simple directions that would change over time. These mice were severely impaired when exposed to even modest amounts of cocaine, amounts so low that “normal” mice were unaffected. They repeatedly performed old failed responses and so failed to win rewards.

“In other words, small deficiencies in cell shape and small amounts of cocaine add up to produce unexpectedly large deficits in behavioral flexibility,” Gourley said.

The same learning and memory processes are thought to allow humans to correct unproductive behavioral patterns.

“This study provides evidence that cell shape achieved during adolescent development may determine the long-term behavioral consequences of even modest amounts of cocaine,” Gourley said. “Without optimal cell shape, even low-dose cocaine may produce poor decision-making strategies that persist into adulthood.”

The study was funded by the National Institutes of Health and the Connecticut Department of Mental Health and Addiction Services.