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Electrical and chemical stimulation of the basolateral complex of the amygdala reinstates cocaine-seeking behavior in the rat

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Abstract

Rationale

The basolateral complex of the amygdala (BLC) is part of a neural circuit that is activated in humans during cocaine craving elicited by exposure to drug-related environmental cues. In animals, the BLC is necessary for cocaine-seeking behavior elicited by cocaine-associated cues. It has not been determined whether BLC activation is sufficient to reinstate cocaine seeking.

Objectives

To determine whether electrical or excitatory amino-acid stimulation of the BLC is sufficient to induce reinstatement of cocaine seeking in rats.

Methods

Rats were catheterized and trained to lever-press for intravenous cocaine infusions on a fixed ratio (FR)-1 schedule of reinforcement. Once baseline cocaine-taking criteria were met, lever-pressing behavior was extinguished by substitution of saline for cocaine. After meeting criteria for extinction, animals were subjected to brief electrical (20 Hz, 400 μA or 2 Hz, 400 μA; 200 pulses per stimulation) or N-methyl-d-aspartate (NMDA; 250 ng/0.5 μl) BLC stimulation and lever pressing behavior was monitored.

Results

Electrical BLC stimulation with 20-Hz produced reinstatement of lever pressing previously associated with cocaine self-administration, while 2-Hz stimulation did not. Electrical stimulation of cerebellar and medial forebrain bundle loci did not reinstate cocaine seeking. Hence, the reinstatement was frequency dependent and anatomically selective. NMDA microinjections into the BLC also reinstated cocaine-seeking behavior.

Conclusions

BLC stimulation is sufficient to reinstate cocaine-seeking behavior in the rat. These results are congruent with the hypothesis that the basolateral complex of the amygdala is part of a neural system mediating drug-seeking behavior.

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Fig. 1A–C.
Fig. 2 A,B.
Fig. 3 A,B.

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Acknowledgements

We thank William Paredes for technical support and George Alheid for helpful discussion of neuroanatomical issues. This work was supported by the Aaron Diamond Foundation; the Julia Sullivan Medical Research Fund; the Old Stones Foundation; the Chemistry and Medical Departments, Brookhaven National Laboratory; and the New York State Office of Alcoholism and Substance Abuse Services. Preparation of the manuscript was additionally supported by the Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health. Data in this paper are from a dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Sue Golding Graduate Division of Medical Sciences, Albert Einstein College of Medicine, Yeshiva University. A preliminary report on parts of this work was presented previously in abstract form (Hayes et al. 1999).

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Authors and Affiliations

  1. Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA

    Robert J. Hayes, Stanislav R. Vorel & Jordan Spector

  2. Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224, USA

    Robert J. Hayes, Stanislav R. Vorel & Eliot L. Gardner

  3. Department of Psychiatry, Albert Einstein College of Medicine, Bronx, NY 10461, USA

    Xinhe Liu

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  1. Robert J. Hayes
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  2. Stanislav R. Vorel
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  4. Xinhe Liu
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  5. Eliot L. Gardner
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Correspondence to Eliot L. Gardner.

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R.J. Hayes and S.R. Vorel contributed equally to the work

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Hayes, R.J., Vorel, S.R., Spector, J. et al. Electrical and chemical stimulation of the basolateral complex of the amygdala reinstates cocaine-seeking behavior in the rat. Psychopharmacology 168, 75–83 (2003). https://doi.org/10.1007/s00213-002-1328-3

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