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


OBJECTIVE
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.
Hayes
Robert J
RJ
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA.|Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224, USA.
Vorel
Stanislav R
SR
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA.|Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224, USA.
Spector
Jordan
J
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Liu
Xinhe
X
Department of Psychiatry, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Gardner
Eliot L
EL
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.
D000679:Amygdala / Q000187:drug effects* / Q000502:physiology*; D000818:Animals; D016739:Behavior, Addictive / Q000139:chemically induced* / Q000523:psychology; D003042:Cocaine / Q000008:administration & dosage*; D004558:Electric Stimulation / Q000379:methods; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012646:Self Administration; D013268:Stimulation, Chemical
D016202:N-Methylaspartate; D003042:Cocaine