A role for nucleus accumbens glutamate transmission in the relapse to cocaine-seeking behavior

Cornish, Jennifer L.; Duffy, Philip E.; Pw, Kalivas

doi:10.1016/s0306-4522(99)00214-6

Cited by 228 publications

(217 citation statements)

References 47 publications

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“…Rats were then placed into the chambers for a 2-h extinction session, during which the light-tone CSs were not presented and responses had no programmed consequences. The 10 mg/kg priming dose of cocaine was selected based on previous studies showing that it produces maximal reinstatement of cocaine seeking (Cornish et al, 1999). The order of TTX vs vehicle infusions was counterbalanced across the two test days based on cocaine intake, and was either the same or reversed as that during the explicit CS-induced reinstatement tests.…”

Section: Experiments 2: Effects Of Dorsal Hippocampus Inactivation On mentioning

confidence: 99%

The Role of the Dorsomedial Prefrontal Cortex, Basolateral Amygdala, and Dorsal Hippocampus in Contextual Reinstatement of Cocaine Seeking in Rats

Fuchs

Evans

Ledford

et al. 2004

Neuropsychopharmacol

488

517

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The present study tested the hypothesis that separate neural substrates mediate cocaine relapse elicited by drug-associated contextual stimuli vs explicit conditioned stimuli (CSs) and cocaine. Specifically, we investigated the involvement of the dorsal hippocampus (DH), basolateral amygdala (BLA), and dorsomedial prefrontal cortex (dmPFC) in contextual reinstatement of cocaine-seeking behavior and the involvement of the DH in explicit CS-and cocaine-induced reinstatement. Rats were trained to self-administer cocaine in a distinct context or in the presence of CSs paired explicitly with cocaine infusions. Responding of context-trained rats was then extinguished in the previously cocaine-paired or an alternate context, whereas responding of explicit CS-trained rats was extinguished in the absence of the CSs. Subsequently, the target brain regions or anatomical control regions were functionally inactivated using tetrodotoxin (0 or 5 ng/ side), and cocaine-seeking behavior (ie, nonreinforced responses) was assessed in the cocaine-paired context, in the alternate context, in the presence of the explicit CSs, or following cocaine priming (10 mg/kg, i.p.). DH inactivation abolished contextual, but failed to alter explicit CS-or cocaine-induced, reinstatement of cocaine-seeking behavior. BLA or dmPFC inactivation also abolished contextual reinstatement. Conversely, inactivation of the control brain regions failed to alter contextual reinstatement. In conclusion, the DH, BLA, and dmPFC play critical roles in contextual reinstatement. Previous findings suggest that the BLA is critical for explicit CS-induced, but not cocaine-primed, reinstatement and the dmPFC is critical for both explicit CS-induced and cocaine-primed reinstatement. Thus, distinct but partially overlapping neural substrates mediate context-induced, explicit CS-induced, and cocaine-primed reinstatement of extinguished cocaine-seeking behavior.

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Section: Experiments 2: Effects Of Dorsal Hippocampus Inactivation On mentioning

confidence: 99%

The Role of the Dorsomedial Prefrontal Cortex, Basolateral Amygdala, and Dorsal Hippocampus in Contextual Reinstatement of Cocaine Seeking in Rats

Fuchs

Evans

Ledford

et al. 2004

Neuropsychopharmacol

488

517

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“…The doses of AMPA were in part selected based on the findings of Cornish et al (1999) and Cornish and Kalivas (2000) showing that cocaine seeking under an FR schedule of reinforcement can be reinstated by 0.4 but not 0.04 nmol/ side of AMPA in the NAcc.…”

Section: Design and Proceduresmentioning

confidence: 99%

“…AMPA receptors appear to be specifically implicated because infusing AMPA into the NAcc reinstates drug seeking (Cornish et al, 1999;Cornish and Kalivas, 2000) while infusion of AMPA receptor antagonists into this site blocks the reinstatement produced by systemic cocaine, NAcc DA, or cocaine in the prefrontal cortex (Cornish and Kalivas, 2000;Park et al, 2002) as well as responding for cocaine-associated cues under a second-order schedule of reinforcement (Di Ciano and Everitt, 2001). NMDA receptor agonists and antagonists have been reported to produce mixed effects (Cornish et al, 1999;Cornish and Kalivas, 2000;Park et al, 2002). Collectively, these findings suggest an essential role for glutamate afferents in the NAcc and local AMPA receptors in particular in the reinstatement of drug seeking by cocaine.…”

Section: Introductionmentioning

confidence: 99%

Previous Exposure to Psychostimulants Enhances the Reinstatement of Cocaine Seeking by Nucleus Accumbens AMPA

Suto

Tanabe

Austin

et al. 2004

Neuropsychopharmacol

103

100

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The effect of previous exposure to psychostimulants on the subsequent self-administration of cocaine as well as reinstatement of this behavior by priming infusions of AMPA into the nucleus accumbens (NAcc) was examined. Rats were exposed to five injections, one injection every third day, of either saline or amphetamine (AMPH: 1.5 mg/kg, i.p.). Starting 10 days later, they were trained to selfadminister cocaine (0.3 mg/kg/infusion, i.v.) and subsequently tested under a progressive ratio (PR) schedule for 4 consecutive days. As expected, rats exposed to AMPH worked more and obtained more cocaine infusions than saline exposed controls on the PR test sessions. Following daily extinction sessions during which saline was substituted for cocaine, the effect of priming infusions of AMPA (0.0, 0.08, or 0.8 nmol/0.5 ml/side) into the NAcc was then examined on two tests: one conducted 4 days after the last cocaine PR test session (2-3 weeks after the last AMPH exposure injection) and the next 4 weeks later. Consistent with previous reports, NAcc AMPA dosedependently reinstated cocaine seeking on both tests regardless of exposure condition. Importantly, this priming effect of NAcc AMPA was significantly enhanced in AMPH compared to saline exposed rats on the first test conducted 2-3 weeks after AMPH. On the second test, conducted 4 weeks after cocaine, reinstatement was similarly enhanced in both groups to levels observed on the first test in AMPH exposed rats. These results indicate that both noncontingent (AMPH) and contingent (cocaine) exposure to psychostimulants enhances the reinstatement of cocaine seeking by NAcc AMPA and appears to do so in a time-dependent manner.

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“…The integrity of the corticoaccumbens glutamate pathway is required for expressing many drug-induced changes in behavior, including the sensitization To whom correspondence should be addressed: Karen K. Szumlinski, Ph.D., Department of Psychology, University of California Santa Barbara, Santa Barbara, CA, USA 93106-9660.of a drug's psychomotor-activating effects [e.g., 28-37], the development of tolerance to a drug's psychomotor-inhibiting effects [e.g., 38,39], drug-conditioned place-preference [e.g., 36,38,40-43], the maintenance of drug self-administration [e.g., [44][45][46] and the reinstatement of drug-seeking [47][48][49][50][51][52][53][54][55][56]. Further, in vivo microdialysis studies have revealed pronounced effects of either acute or repeated drug-induced changes in NAC or PFC extracellular levels of glutamate by a number of drugs of abuse, including: cocaine [e.g., 31,35,37, 47,53,57,58], amphetamines [e.g., 20,59,60-62, but see 63], alcohol [38,39,64], nicotine [65][66][67][68] and opiates [69,70], implicating drug-induced changes in presynaptic aspects of corticoaccumbens glutamate transmission in mediating the changes in behavior produced by drugs of abuse.…”

Section: Introductionmentioning

confidence: 99%

Homers regulate drug-induced neuroplasticity: Implications for addiction

Szumlinski

Ary

Lominac

2008

Biochemical Pharmacology

118

160

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Drug addiction is a chronic, relapsing disorder, characterized by an uncontrollable motivation to seek and use drugs. Converging clinical and preclinical observations implicate pathologies within the corticolimbic glutamate system in the genetic predisposition to, and the development of, an addicted phenotype. Such observations pose cellular factors regulating glutamate transmission as likely molecular candidates in the etiology of addiction. Members of the Homer family of proteins regulate signal transduction through, and the trafficking of, glutamate receptors, as well as maintain and regulate extracellular glutamate levels in corticolimbic brain regions. This review summarizes the existing data implicating the Homer family of protein in acute behavioral and neurochemical sensitivity to drugs of abuse, the development of drug-induced neuroplasticity, as well as other behavioral and cognitive pathologies associated with an addicted state.

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A role for nucleus accumbens glutamate transmission in the relapse to cocaine-seeking behavior

Cited by 228 publications

References 47 publications

The Role of the Dorsomedial Prefrontal Cortex, Basolateral Amygdala, and Dorsal Hippocampus in Contextual Reinstatement of Cocaine Seeking in Rats

The Role of the Dorsomedial Prefrontal Cortex, Basolateral Amygdala, and Dorsal Hippocampus in Contextual Reinstatement of Cocaine Seeking in Rats

Previous Exposure to Psychostimulants Enhances the Reinstatement of Cocaine Seeking by Nucleus Accumbens AMPA

Homers regulate drug-induced neuroplasticity: Implications for addiction

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