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The Journal of Neuroscience, December 19, 2007, 27(51):14179-14189; doi:10.1523/JNEUROSCI.4477-07.2007

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Behavioral/Systems/Cognitive
Repeated Electrical Stimulation of Reward-Related Brain Regions Affects Cocaine But Not "Natural" Reinforcement

Dino Levy,^1 * Maytal Shabat-Simon,^1,3 * Uri Shalev,² Noam Barnea-Ygael,¹ Ayelet Cooper,¹ and Abraham Zangen¹

¹Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel, ²Department of Psychology, Concordia University, Montreal, Quebec, Canada H4B 1R6, and ³Department of Physiology and Pharmacology, Tel-Aviv University, Tel-Aviv 69978, Israel

Correspondence should be addressed to Dr. Abraham Zangen, Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel. Email: a.zangen{at}weizmann.ac.il

Drug addiction is associated with long-lasting neuronal adaptations including alterations in dopamine and glutamate receptors in the brain reward system. Treatment strategies for cocaine addiction and especially the prevention of craving and relapse are limited, and their effectiveness is still questionable. We hypothesized that repeated stimulation of the brain reward system can induce localized neuronal adaptations that may either potentiate or reduce addictive behaviors. The present study was designed to test how repeated interference with the brain reward system using localized electrical stimulation of the medial forebrain bundle at the lateral hypothalamus (LH) or the prefrontal cortex (PFC) affects cocaine addiction-associated behaviors and some of the neuronal adaptations induced by repeated exposure to cocaine. Repeated high-frequency stimulation in either site influenced cocaine, but not sucrose reward-related behaviors. Stimulation of the LH reduced cue-induced seeking behavior, whereas stimulation of the PFC reduced both cocaine-seeking behavior and the motivation for its consumption. The behavioral findings were accompanied by glutamate receptor subtype alterations in the nucleus accumbens and the ventral tegmental area, both key structures of the reward system. It is therefore suggested that repeated electrical stimulation of the PFC can become a novel strategy for treating addiction.

Key words: cocaine; addiction; intracranial electrical stimulation; self-administration; lateral hypothalamus; prefrontal cortex

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Received May 21, 2007; revised Oct. 31, 2007; accepted Oct. 31, 2007.

Correspondence should be addressed to Dr. Abraham Zangen, Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel. Email: a.zangen{at}weizmann.ac.il

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