Researchers have known that certain experiences, such as those involved in learning, can physically change brain structure and affect behavior. Now, a study of rats has shown that exposure to stimulant drugs such as amphetamine or cocaine can impair plasticity as a consequence of experience. “The findings from this study indicate that at least some of the cognitive and behavioral advantages that accrue with experience may be diminished by prior exposure to psychostimulant drugs,” said lead investigator Bryan Kolb, PhD, Professor of Psychology and Neuroscience at the University of Lethbridge in Alberta. “This impairment of the ability of specific brain circuits to change in response to experiences may help explain some of the behavioral and cognitive deficits seen in individuals who are addicted to drugs.”

Dr. Kolb’s team conducted a series of experiments to examine how drugs of abuse might interact with life experiences to produce changes in brain structure. They administered amphetamine, cocaine, or saline repeatedly for 20 days to individually housed rats. Previously, this pattern of drug administration had been shown to produce both behavioral changes in response to the drugs and structural changes in several brain regions. However, in the current study, the researchers went one step further.

After the 20-day drug exposure, the rats were housed in a new environment for three to three and one-half months. Half the drug- and saline-injected animals were placed in standard laboratory cages. The other animals in each group were housed in a complex environment that contained a variety of stimuli—multiple levels with ramps, bridges, a climbing chain, tunnels, and toys that were rearranged once a week to encourage continued exploration of the environment. Afterward, the rats’ brains were analyzed for changes in dendritic branching and spine density. Specifically, the researchers examined the spiny neurons in the nucleus accumbens and the pyramidal cells in the parietal cortex. These areas had been shown in previous studies to be altered by experience and/or drugs of abuse.

STRUCTURAL CHANGES

Dr. Kolb’s team found that amphetamine exposure increased dendritic branching and spine density in the nucleus accumbens and decreased spine density in the parietal cortex. Exposure to the complex environment also increased the dendritic branching and spine density in the nucleus accumbens and, in contrast to amphetamine, increased dendritic branching and spine density in the parietal cortex as well. Animals that had been given amphetamine and were then placed in the complex environment did not show the same environmentally induced structural changes in the nucleus accumbens and parietal cortex as did saline-treated animals in the complex environment. Results for the animals treated with cocaine were similar, in that prior treatment with cocaine blocked the environmentally induced changes in the medium spiny neurons of the nucleus accumbens, the only region examined.

“On most measures, prior treatment with amphetamine or cocaine interfered with the ability of experience in a complex environment to increase dendritic arborization and spine density,” the researchers reported in the September 2 Proceedings of the National Academy of Sciences. “[I]n some brain regions, repeated exposure to psychomotor-stimulant drugs limits the ability of later experience to produce this form of synaptic plasticity, which may contribute to the persistent behavioral and cognitive deficits associated with drug abuse.”

IMPORTANT IMPLICATIONS

“More research is warranted to determine whether certain experiences, such as exposure to complex or rewarding environments, can alter the ability of drugs to induce structural changes in the brain,” said Dr. Kolb. “If exposure to psychostimulant drugs can alter the effects of subsequent experience, experience may be able to influence the later effects of drugs. It may even be possible for certain experiences to counteract the effects of psychostimulant drugs.”

Suggested Reading
Kolb B, Gorny G, Li Y, et al. Amphetamine or cocaine limits the ability of later experience to promote structural plasticity in the neocortex and nucleus accumbens. Proc Natl Acad Sci USA. 2003;100:10523-10528.

Return to table of contents