Limbic and Motor Circuitry Underlying Footshock-Induced Reinstatement of Cocaine-Seeking Behavior

The role of limbic, cortical, and striatal circuitry in a footshock reinstatement model of relapse to cocaine seeking was evaluated. Transient inhibition of the central extended amygdala [CEA; including the central nucleus of the amygdala (CN), ventral bed nucleus of the stria terminalis (BNSTv), an...

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Bibliographic Details
Published in:	The Journal of neuroscience Vol. 24; no. 7; pp. 1551 - 1560
Main Authors:	McFarland, Krista, Davidge, Susan B, Lapish, Christopher C, Kalivas, Peter W
Format:	Journal Article
Language:	English
Published:	United States Soc Neuroscience 18-02-2004 Society for Neuroscience
Subjects:	Amygdala - drug effects Amygdala - physiopathology Animals Behavioral/Systems/Cognitive Cocaine - administration & dosage Cocaine - pharmacology Cocaine-Related Disorders - physiopathology Conditioning, Operant - drug effects Conditioning, Operant - physiology Disease Models, Animal Dopamine - metabolism Dopamine Antagonists - pharmacology Efferent Pathways - drug effects Efferent Pathways - physiopathology Electroshock GABA Agonists - pharmacology Globus Pallidus - physiology Glutamic Acid - metabolism Limbic System - drug effects Limbic System - physiology Male Microinjections Motor Activity - drug effects Neostriatum - drug effects Neostriatum - physiopathology Neural Inhibition - drug effects Neural Inhibition - physiology Nucleus Accumbens - physiology Prefrontal Cortex - drug effects Prefrontal Cortex - physiopathology Rats Rats, Sprague-Dawley Recurrence Self Administration Septal Nuclei - physiology Ventral Tegmental Area
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Summary:	The role of limbic, cortical, and striatal circuitry in a footshock reinstatement model of relapse to cocaine seeking was evaluated. Transient inhibition of the central extended amygdala [CEA; including the central nucleus of the amygdala (CN), ventral bed nucleus of the stria terminalis (BNSTv), and nucleus accumbens shell (NAshell)], ventral tegmental area (VTA), and motor circuitry [including the dorsal prefrontal cortex (PFCd), nucleus accumbens core (NAcore), and ventral pallidum (VP)] blocked the ability of footshock stress to reinstate lever pressing previously associated with cocaine delivery. However, inhibition of the basolateral amygdala, mediodorsal nucleus of the thalamus, or the ventral prefrontal cortex had no effect on drug-seeking behavior. These data suggest that footshock stress activates limbic circuitry of the CEA that, via the VTA, activates motor output circuitry responsible for producing lever press responding. Consistent with this notion, the D1/D2 dopamine receptor antagonist fluphenazine blocked footshock-induced reinstatement when infused into the PFCd. Further, inhibition of the NAshell blocked a footshock-induced increase in dopamine within the PFC and concomitantly blocked reinstatement responding. Also supporting the idea of a CEA-VTA-motor circuit in stress-induced reinstatement of cocaine seeking, inactivation of the PFCd was shown to block stress-induced glutamate release within the NAcore while concurrently inhibiting reinstatement responding. Taken together, these data suggest that footshock activates limbic circuitry in the CEA, which in turn activates a VTA dopamine projection to the PFCd. The rise in dopamine within the PFCd initiates reinstatement via a glutamatergic projection to the NAcore.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0270-6474 1529-2401
DOI:	10.1523/JNEUROSCI.4177-03.2004