Glutamate Transmission in the Nucleus Accumbens Mediates Relapse in Cocaine Addiction

Cornish, Jennifer L.; Kalivas, Peter W.

doi:10.1523/jneurosci.20-15-j0006.2000

Cited by 474 publications

(444 citation statements)

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“…As such, it is reasonable to suspect that NAcc DA may also underlie the ability of noncontingent injections of these drugs to reinstate extinguished self-administration behavior. Consistent with this view, systemic priming injections of DA receptor agonists (Wise et al, 1990;Self et al, 1996) or noncontingent infusions of DA into the NAcc (Cornish and Kalivas, 2000) reinstate cocaine seeking. Curiously, however, infusing a DA receptor antagonist into the NAcc blocks the reinstatement of cocaine seeking by NAcc DA (Cornish and Kalivas, 2000) but not by systemic cocaine (Cornish and Kalivas, 2000;McFarland and Kalivas, 2001).…”

Section: Introductionmentioning

confidence: 73%

“…Consistent with this view, systemic priming injections of DA receptor agonists (Wise et al, 1990;Self et al, 1996) or noncontingent infusions of DA into the NAcc (Cornish and Kalivas, 2000) reinstate cocaine seeking. Curiously, however, infusing a DA receptor antagonist into the NAcc blocks the reinstatement of cocaine seeking by NAcc DA (Cornish and Kalivas, 2000) but not by systemic cocaine (Cornish and Kalivas, 2000;McFarland and Kalivas, 2001). These results, together with others showing that cocaine infused into the NAcc or prefrontal cortex reinstates drug seeking (Park et al, 2002), suggest that actions of cocaine other than its increase of extracellular levels of NAcc DA are involved.…”

Section: Introductionmentioning

confidence: 73%

“…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%

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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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Section: Introductionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 73%

Section: Design and Proceduresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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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“…Within the NAc, KOP receptor agonists inhibit the release of glutamate (Yuan et al, 1992;Hjelmstad andFields, 2001, 2003). DA signaling in the prefrontal cortex and glutamate signaling in the NAc have both been implicated in drug relapse (Cornish and Kalivas, 2000;McFarland and Kalivas, 2001;McFarland et al, 2003). Thus, the localization as well as behavioral actions of KOP receptors makes them an inviting therapeutic target for the treatment of addiction.…”

Section: Introductionmentioning

confidence: 99%

Acute Amphetamine Exposure Selectively Desensitizes κ-Opioid Receptors in the Nucleus Accumbens

Xia

Whistler

et al. 2007

Neuropsychopharmacol

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In the present study, we investigated the effects of psychostimulant exposure on k-opioid peptide (KOP) receptor signaling in the rat mesolimbic system. A single subcutaneous (s.c.) injection of amphetamine (2.5 mg/kg) reduced the KOP receptor-mediated inhibition of glutamate release in the nucleus accumbens shell, as a consequence of KOP receptor desensitization. This effect was blocked by dopamine (DA) receptor antagonists or the nonselective opioid antagonist, naltrexone (1 mg/kg, s.c.), and mimicked by the KOP receptor agonists U69593 (0.32 mg/kg, s.c.) and dynorphin (1 mM), indicating that an amphetamine-induced release of dynorphin is producing a long-lasting desensitization of the KOP receptor. Despite the fact that amphetamine also increases dynorphin release in the ventral tegmental area (VTA), KOP receptor function in this region was not affected by amphetamine; there was no difference in the KOP receptor-mediated change in firing rate or resting membrane potential measured in VTA neurons from saline-or amphetaminetreated animals. This study demonstrates that amphetamine can produce regionally selective adaptations in KOP receptor signaling, which may, in turn, alter the effects of subsequent drug exposure.

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Motivational Systems

McFarland¹,

Kalivas²

2003

Handbook of Psychology

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The present chapter reviews the behavioral, anatomical, and neurobiological evidence regarding the neural substrates of motivated behavior. This involves examination of motivational circuitry within the basal forebrain. The motive circuit consists of two parallel subcircuits: one predominantly associated with motor function and the other primarily associated with limbic functions. It is hypothesized that the motor circuit is critical for the production of well‐learned behavioral responses, while the limbic circuit is important for processing environmental stimuli and transmitting this information to portions of the motor circuit, thus instigating adaptive motor responses. Within this circuit, dopamine, glutamate, GABA, and neuropeptides are neurotransmitters, each conveying potentially distinct information. The present review is organized around these neruotransmitters in reference to the following hypotheses: 1. Glutamate stimulates behavior and the anatomical origin of the activated glutamatergic afferents provides motor memory to provoke the appropriate behavioral response. In addition, under the appropriate conditions glutamate transmission promotes neuroplasticity permitting learning and behavioral adaptations to occur. 2. Dopamine supports plasticity and learning by engaging the appropriate cellular machinery to modify neuronal communication, especially excitatory transmission. 3. GABA regulates overall circuit tone and thereby serves to ‘bind’ or sustain an animal's motivational state until the goal object can be achieved. 4. Neuropeptides contribute to subjective valence. Thus, the neuroanatomical and neurochemical organization of the motive circuit provides the neural basis of motivation and reinforcement and functions to elicit adaptive motor responses in the presence of motivationally significant stimuli.

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Glutamate Transmission in the Nucleus Accumbens Mediates Relapse in Cocaine Addiction

Cited by 474 publications

References 47 publications

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

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

Acute Amphetamine Exposure Selectively Desensitizes κ-Opioid Receptors in the Nucleus Accumbens

Motivational Systems

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