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The Journal of Neuroscience, September 14, 2005, 25(37):8407-8415; doi:10.1523/JNEUROSCI.1910-05.2005

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Behavioral/Systems/Cognitive
Subthalamic Nucleus Lesions Enhance the Psychomotor-Activating, Incentive Motivational, and Neurobiological Effects of Cocaine

Jason M. Uslaner, Pengwei Yang, and Terry E. Robinson

Biopsychology and Neuroscience Programs, Department of Psychology, University of Michigan, Ann Arbor, Michigan 48019-1109

The subthalamic nucleus (STN) is traditionally thought to be involved in motor control, and dysfunction of the STN is thought to contribute to movement disorders. Here, we show that the STN also plays an important role in motivational processes and the response to drugs of abuse. Specifically, bilateral STN lesions produced a dose-dependent increase in the psychomotor-activating effects of cocaine, the rate at which animals acquired cocaine self-administration, and the motivation for cocaine assessed using a progressive ratio schedule. Furthermore, bilateral STN lesions enhanced the ability of cocaine to induce gene expression in the nucleus accumbens and caudate–putamen, two structures known to be involved in mediating the psychomotor-activating and incentive motivational effects of drugs of abuse. These findings suggest that engagement of the STN serves to dampen the psychomotor-activating and incentive motivational effects of drugs of abuse. Thus, the STN may serve as a novel target for therapeutic interventions aimed at treating drug dependence.

Key words: nucleus accumbens; caudate–putamen; c-fos; progressive ratio; acquisition; self-administration

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Received May 12, 2005; revised August 2, 2005; accepted August 2, 2005.

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