Robert J Hayes1,2, Stanislav R Vorel1,2, Jordan Spector1, Xinhe Liu3, Eliot L Gardner4. 1. Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA. 2. Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224, USA. 3. Department of Psychiatry, Albert Einstein College of Medicine, Bronx, NY 10461, USA. 4. Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224, USA. egardner@intra.nida.nih.gov.
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 microA or 2 Hz, 400 microA; 200 pulses per stimulation) or N-methyl- d-aspartate (NMDA; 250 ng/0.5 microl) 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.
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 microA or 2 Hz, 400 microA; 200 pulses per stimulation) or N-methyl- d-aspartate (NMDA; 250 ng/0.5 microl) 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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