Joselyn McLaughlin1, Ronald E See2. 1. Department of Physiology and Neuroscience, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA, USA. 2. Department of Physiology and Neuroscience, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA, USA. seere@musc.edu.
Abstract
RATIONALE: Environmental stimuli previously paired with cocaine can induce craving in humans and reinstate extinguished cocaine-seeking behavior in laboratory animals. Previous evidence has implicated the amygdala and the prefrontal cortex (PFC) as possible substrates for conditioned-cued relapse. OBJECTIVES: In order to test directly the role of the PFC in a model of relapse, the present study examined the effects of reversible inactivation of three medial PFC areas, the anterior cingulate (ACing), the prelimbic cortex (PL), and the infralimbic cortex (IL), on the expression of conditioned-cued reinstatement of extinguished cocaine-seeking behavior. We also tested the involvement of the basolateral amygdala (BLA) and the parietal cortex immediately dorsal to the BLA, sensory cortex area 1 - barrel field (S1BF). METHODS: During daily 3-h sessions, rats pressed a lever for IV cocaine infusions that were paired with a light-tone (LT) presentation. Following extinction of lever pressing in the absence of the LT, reinstatement of extinguished lever pressing was measured during response-contingent presentations of the LT in the absence of cocaine. For localized reversible inactivation, tetrodotoxin (TTX) (5 ng/0.5 micro l/side) or vehicle was bilaterally infused just prior to reinstatement testing. RESULTS: TTX inactivation of the BLA, ACing, or PL impaired the ability of LT presentations to reinstate extinguished lever pressing for cocaine-paired stimuli. In contrast, inactivation of the IL or the S1BF had no effect on conditioned-cued reinstatement. Furthermore, there was no effect of TTX in any of the tested brain regions on general locomotor activity. CONCLUSIONS. These results support a role for the dorsomedial PFC and the BLA in the circuitry that mediates drug-seeking behavior elicited by cocaine-associated stimuli. Placed within the context of recent studies using drug-primed and stress-induced reinstatement models, we suggest that the dorsomedial PFC may serve as a common link in the neural circuitry underlying reinstatement of drug-seeking behavior.
RATIONALE: Environmental stimuli previously paired with cocaine can induce craving in humans and reinstate extinguished cocaine-seeking behavior in laboratory animals. Previous evidence has implicated the amygdala and the prefrontal cortex (PFC) as possible substrates for conditioned-cued relapse. OBJECTIVES: In order to test directly the role of the PFC in a model of relapse, the present study examined the effects of reversible inactivation of three medial PFC areas, the anterior cingulate (ACing), the prelimbic cortex (PL), and the infralimbic cortex (IL), on the expression of conditioned-cued reinstatement of extinguished cocaine-seeking behavior. We also tested the involvement of the basolateral amygdala (BLA) and the parietal cortex immediately dorsal to the BLA, sensory cortex area 1 - barrel field (S1BF). METHODS: During daily 3-h sessions, rats pressed a lever for IV cocaine infusions that were paired with a light-tone (LT) presentation. Following extinction of lever pressing in the absence of the LT, reinstatement of extinguished lever pressing was measured during response-contingent presentations of the LT in the absence of cocaine. For localized reversible inactivation, tetrodotoxin (TTX) (5 ng/0.5 micro l/side) or vehicle was bilaterally infused just prior to reinstatement testing. RESULTS:TTX inactivation of the BLA, ACing, or PL impaired the ability of LT presentations to reinstate extinguished lever pressing for cocaine-paired stimuli. In contrast, inactivation of the IL or the S1BF had no effect on conditioned-cued reinstatement. Furthermore, there was no effect of TTX in any of the tested brain regions on general locomotor activity. CONCLUSIONS. These results support a role for the dorsomedial PFC and the BLA in the circuitry that mediates drug-seeking behavior elicited by cocaine-associated stimuli. Placed within the context of recent studies using drug-primed and stress-induced reinstatement models, we suggest that the dorsomedial PFC may serve as a common link in the neural circuitry underlying reinstatement of drug-seeking behavior.
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