Deep brain stimulation of the nucleus accumbens shell attenuates cocaine priming-induced reinstatement of drug seeking in rats.

Full Abstract

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 muA. 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.

Author information

Author/s: Vassoler, Fair M (FM); Schmidt, Heath D (HD); Gerard, Mary E (ME); Famous, Katie R (KR); Ciraulo, Domenic A (DA); Kornetsky, Conan (C); Knapp, Clifford M (CM); Pierce, R Christopher (RC);

Affiliation: Department of Pharmacology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.

Grants: F30 DA19304 (Agency:NIDA NIH HHS) ; F31 DA16824 (Agency:NIDA NIH HHS) ; K02 DA018678-03 (Agency:NIDA NIH HHS) ; K02 DA18678 (Agency:NIDA NIH HHS) ; K05 DA00099 (Agency:NIDA NIH HHS) ; R01 DA015214-06A1 (Agency:NIDA NIH HHS) ; R01 DA022339-01A2 (Agency:NIDA NIH HHS) ; R01 DA15214 (Agency:NIDA NIH HHS) ; T32 GM008541-7 (Agency:NIGMS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)

Reference: 2008-Aug; vol 28 (issue 35) : pp 8735-9

Dates: Created 2008/08/28; Completed 2008/09/18; Revised 2009/03/03;

PMID: 18753374, status: MEDLINE (last retrieved date: 3/10/2009)

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