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The Journal of Neuroscience, August 27, 2008, 28(35):8735-8739; doi:10.1523/JNEUROSCI.5277-07.2008

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Brief Communications
Deep Brain Stimulation of the Nucleus Accumbens Shell Attenuates Cocaine Priming-Induced Reinstatement of Drug Seeking in Rats

Fair M. Vassoler,¹ Heath D. Schmidt,³ Mary E. Gerard,² Katie R. Famous,¹ Domenic A. Ciraulo,² Conan Kornetsky,^1,2 Clifford M. Knapp,² and R. Christopher Pierce^1,2

Departments of ¹Pharmacology and ²Psychiatry, Boston University School of Medicine, Boston, Massachusetts 02118, and ³Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06508

Correspondence should be addressed to R. Christopher Pierce, Department of Pharmacology, L603, Boston University School of Medicine, Boston, MA 02118. Email: rcpierce{at}bu.edu

Increasing evidence suggests that deep brain stimulation (DBS), which is currently being used as a therapy for neurological diseases, may be effective in the treatment of psychiatric disorders as well. Here, we examined the influence of DBS of the nucleus accumbens shell on cocaine priming-induced reinstatement of drug seeking, an animal model of relapse. Rats were allowed to self-administer cocaine (0.25 mg, i.v.) 2 h daily for 21 d and then cocaine-seeking behavior was extinguished by replacing cocaine with saline. During the reinstatement phase, DBS was administered bilaterally to the nucleus accumbens shell through bipolar stainless steel electrodes. Biphasic symmetrical pulses were delivered at a frequency of 160 Hz and a current intensity of 150 µA. DBS began immediately after a priming injection of cocaine (0, 5, 10, or 20 mg/kg, i.p.) and continued throughout each 2 h reinstatement session. Results indicated that only the higher doses of cocaine (10 and 20 mg/kg) produced robust and reliable reinstatement of cocaine seeking. DBS of the nucleus accumbens shell significantly attenuated the reinstatement of drug seeking precipitated by these higher cocaine doses. Additional experiments indicated that this DBS effect was both anatomically and reinforcer specific. Thus, DBS of the dorsal striatum had no influence on cocaine reinstatement and DBS of the accumbens shell did not affect the reinstatement of food seeking. Together, these results suggest that DBS of the nucleus accumbens shell may be a potential therapeutic option in the treatment of severe cocaine addiction.

Key words: deep brain stimulation; relapse; addiction; psychostimulant; striatum; accumbens shell

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Received Nov. 28, 2007; revised July 16, 2008; accepted July 19, 2008.

Correspondence should be addressed to R. Christopher Pierce, Department of Pharmacology, L603, Boston University School of Medicine, Boston, MA 02118. Email: rcpierce{at}bu.edu

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