PT  - JOURNAL ARTICLE
AU  - Krista McFarland
AU  - Susan B. Davidge
AU  - Christopher C. Lapish
AU  - Peter W. Kalivas
TI  - Limbic and Motor Circuitry Underlying Footshock-Induced Reinstatement of Cocaine-Seeking Behavior
AID  - 10.1523/JNEUROSCI.4177-03.2004
DP  - 2004 Feb 18
TA  - The Journal of Neuroscience
PG  - 1551--1560
VI  - 24
IP  - 7
4099  - http://www.jneurosci.org/content/24/7/1551.short
4100  - http://www.jneurosci.org/content/24/7/1551.full
SO  - J. Neurosci.2004 Feb 18; 24
AB  - 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.