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Volume 17, Number 21,
Issue of November 1, 1997
pp. 8491-8497
Copyright ©1997 Society for Neuroscience
Persistent Structural Modifications in Nucleus Accumbens and
Prefrontal Cortex Neurons Produced by Previous Experience with
Amphetamine
Received June 23, 1997; revised Aug. 5, 1997; accepted Aug. 13, 1997.
Terry E. Robinson1 and
Bryan Kolb2
1 Department of Psychology and Neuroscience Program,
The University of Michigan, Ann Arbor, Michigan 48109, and
2 Department of Psychology, University of Lethbridge,
Lethbridge, Alberta T1K 3M4, Canada
Experience-dependent changes in behavior are thought to involve
structural modifications in the nervous system, especially alterations
in patterns of synaptic connectivity. Repeated experience with drugs of
abuse can result in very long-lasting changes in behavior, including a
persistent hypersensitivity (sensitization) to their psychomotor
activating and rewarding effects. It was hypothesized, therefore, that
repeated treatment with the psychomotor stimulant drug amphetamine,
which produces robust sensitization, would produce structural
adaptations in brain regions that mediate its psychomotor activating
and rewarding effects. Consistent with this hypothesis, it was found
that amphetamine treatment altered the morphology of neurons in the
nucleus accumbens and prefrontal cortex. Exposure to amphetamine
produced a long-lasting (>1 month) increase in the length of
dendrites, in the density of dendritic spines, and in the number of
branched spines on the major output cells of the nucleus accumbens, the
medium spiny neurons, as indicated by analysis of Golgi-stained
material. Amphetamine treatment produced similar effects on the apical
(but not basilar) dendrites of layer III pyramidal neurons in the
prefrontal cortex. The ability of amphetamine to alter patterns of
synaptic connectivity in these structures may contribute to some of the
long-term behavioral consequences of repeated amphetamine use,
including amphetamine psychosis and addiction.
Key words:
amphetamine;
sensitization;
Golgi staining;
nucleus
accumbens;
prefrontal cortex;
plasticity;
psychostimulant drugs
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