Dissociation of Primary and Secondary Reward-Relevant Limbic Nuclei in an Animal Model of Relapse

Grimm, Jeffrey W.; See, Ronald E.

doi:10.1016/s0893-133x(99)00157-8

Cited by 196 publications

(182 citation statements)

References 36 publications

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“…The voltage-dependent sodium channel blocker TTX, an agent that temporarily inhibits impulse generation and neural conductance (Narahashi, 1972), has been utilized as a reversible neural inactivating agent in numerous behavioral studies (eg Fuchs et al, 2005Fuchs et al, , 2006Grimm and See, 2000;Harlan et al, 1983). In the current study, TTX was not directly administered into the CA1 region of the hippocampus, which would have ruled out a direct role of the CA1 in the acquisition of cocaine-seeking.…”

Section: Discussionmentioning

confidence: 99%

The Dorsal Subiculum Mediates the Acquisition of Conditioned Reinstatement of Cocaine-Seeking

Martin‐Fardon

Ciccocioppo

Aujla

et al. 2007

Neuropsychopharmacol

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Contextual stimuli present during a single lifetime cocaine self-administration experience acquire occasion-setting actions sufficient to persistently elicit cocaine-seeking behavior in rats, with effects lasting nearly 1 year. The goal of this study was to identify neural substrates mediating the acquisition of drug-related conditioning taking place during a single cocaine self-administration experience with focus on the subicular formation, a brain site that has been implicated in associative learning relevant for conditioned reward-seeking including conditioned reinstatement. Male Wistar rats were given 2 h of response-contingent access to intravenous cocaine or saline in the presence of distinct stimuli that served as contextual stimuli associated with the availability and subjective effects of cocaine (S + ) vs saline (S À ). Before onset of the sessions, rats received bilateral microinjections of tetrodotoxin (TTX) into the ventral subiculum (VSUB) or dorsal subiculum (DSUB). Following extinction of responding by withholding cocaine, rats were subjected to reinstatement tests in which exposure to the cocaine-(but not saline) associated stimulus produced strong recovery of responding. This effect was completely abolished in rats with transient TTX inactivation of the DSUB during the conditioning session. TTX inactivation of the VSUB during conditioning did not alter the response-reinstating effects of the cocaine cue. The results suggest that functional integrity of the DSUB, but not VSUB, is critical for the acquisition of conditioned cocaine-seeking controlled by contextual stimuli under conditions where such learning occurs during a single conditioning trial.

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Section: Discussionmentioning

confidence: 99%

The Dorsal Subiculum Mediates the Acquisition of Conditioned Reinstatement of Cocaine-Seeking

Martin‐Fardon

Ciccocioppo

Aujla

et al. 2007

Neuropsychopharmacol

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“…Furthermore, ERKs have been shown to be activated in the central amygdala (CeA) after cue-induced relapse to cocaine seeking and inhibition of ERKs in the CeA decreased cocaine seeking after drug withdrawal (Lu et al, 2005). All these observations suggest that molecular alterations in the amygdala may be involved in cue-induced relapse to drug seeking (Grimm and See, 2000;Yun and Fields, 2003). However, the activation of transcription factors and signaling cascades in the amygdala has never been analyzed in detail in animal models of relapse to alcohol seeking.…”

Section: Introductionmentioning

confidence: 99%

Alcohol Relapse Induced by Discrete Cues Activates Components of AP-1 Transcription Factor and ERK Pathway in the Rat Basolateral and Central Amygdala

Radwańska

Wróbel

Korkosz

et al. 2007

Neuropsychopharmacol

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Alcohol-related cues may induce relapse to heavy alcohol drinking and promote molecular adaptations in discrete brain regions. An exact nature of these molecular alterations is still unknown. In the present study, rats trained to self-administer ethanol were tested for cueinduced reinstatement of ethanol seeking after 30 days of abstinence. Next, a detailed immunocytochemical analysis of c-Fos activation was performed within seven nuclei of the amygdala. In the second experiment, c-Fos activation after reinstatement of ethanol seeking induced by discrete cues was compared with the activation pattern of its putative partner (c-Jun) and regulators (extracellular signalregulated kinases and c-Jun N-terminal kinases). Reexposure to ethanol-associated context cues (an extinction session) potentiated c-Fos expression within the basolateral and central amygdala. Repeated presentation of ethanol-associated discrete cues in an extinction/ reinstatement session led to even stronger c-Fos activation in the latter nuclei. In the second experiment, reexposure to the ethanolassociated context and discrete cues activated both c-Jun and extracellular signal-regulated kinases (ERK1/2) in the basolateral amygdala. Our observations suggest that the basolateral and central amygdala may be specifically involved in alcohol-seeking behavior induced by discrete cues.

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“…For example, one early report identified that the basolateral region of the amygdala as being critical for the reinstatement response to conditioned stimuli (CS) priming [19]. Subsequently, Grimm & See [13] demonstrated that inactivation of the nucleus accumbens was effective in preventing drug (cocaine) induced drug seeking, but had no effect on CS induced priming of reinstatement. The opposite relationship was found to exist for inactivation of the basolateral amygdala, as tetrodotoxin infusion did not affect drug primed reinstatement.…”

Section: Introductionmentioning

confidence: 99%

The effects of extinction training in reducing the reinstatement of drug-seeking behavior: Involvement of NMDA receptors

Kelamangalath

Swant

Stramiello

et al. 2007

Behavioural Brain Research

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Although the process of extinction has been well documented for various forms of behavioral responses, the effects of extinction on the reinstatement of drug seeking behavior are relatively understudied. In this report, the effectiveness of an extinction training protocol to reduce primed reinstatement responses was compared with the effectiveness of an equivalent period of enforced abstinence. We found that extinction training performed in the drug taking environment significantly reduced reinstatement behavior subsequently primed by either contextual cues, conditioned cues, or cocaine infusion. The ability of extinction to reduce cocaine primed reinstatement was blocked by the systemic administration of the competitive NMDAR antagonist ((±)CPP, 5 mg/kg i.p.) administered prior to each extinction training session. Interestingly, this pharmacological intervention had no impact on the effectiveness of extinction to reduce drug-seeking behavior primed by either contextual cues or conditioned cues. These results suggest that an extinction training experience involves multiple mechanisms that can be dissociated into nonNMDAR and NMDAR dependent components with respect to the type of reinstatement (i.e. context-, CS-, or drug-induced) being assessed.

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Dissociation of Primary and Secondary Reward-Relevant Limbic Nuclei in an Animal Model of Relapse

Cited by 196 publications

References 36 publications

The Dorsal Subiculum Mediates the Acquisition of Conditioned Reinstatement of Cocaine-Seeking

The Dorsal Subiculum Mediates the Acquisition of Conditioned Reinstatement of Cocaine-Seeking

Alcohol Relapse Induced by Discrete Cues Activates Components of AP-1 Transcription Factor and ERK Pathway in the Rat Basolateral and Central Amygdala

The effects of extinction training in reducing the reinstatement of drug-seeking behavior: Involvement of NMDA receptors

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