» Articles » PMID: 17652583

Cocaine Experience Controls Bidirectional Synaptic Plasticity in the Nucleus Accumbens

Overview
Journal J Neurosci
Specialty Neurology
Date 2007 Jul 27
PMID 17652583
Citations 258
Authors
Affiliations
Soon will be listed here.
Abstract

Plasticity of glutamatergic synapses is a fundamental mechanism through which experience changes neural function to impact future behavior. In animal models of addiction, glutamatergic signaling in the nucleus accumbens (NAc) exerts powerful control over drug-seeking behavior. However, little is known about whether, how or when experience with drugs may trigger synaptic plasticity in this key nucleus. Using whole-cell synaptic physiology in NAc brain slices, we demonstrate that a progression of bidirectional changes in glutamatergic synaptic strength occurs after repeated in vivo exposure to cocaine. During a protracted drug-free period, NAc neurons from cocaine-experienced mice develop a robust potentiation of AMPAR-mediated synaptic transmission. However, a single re-exposure to cocaine during extended withdrawal becomes a potent stimulus for synaptic depression, abruptly reversing the initial potentiation. These enduring modifications in AMPAR-mediated responses and plasticity may provide a neural substrate for disrupted processing of drug-related stimuli in drug-experienced individuals.

Citing Articles

Cationic peptides cause memory loss through endophilin-mediated endocytosis.

Stokes E, Vasquez J, Azouz G, Nguyen M, Tierno A, Zhuang Y Nature. 2025; 638(8050):479-489.

PMID: 39814881 DOI: 10.1038/s41586-024-08413-w.


Critical Involvement of Actin Stabilizer TMOD2 in Cocaine-Induced Neuroadaptations.

Nogueira M J Neurosci. 2024; 44(49).

PMID: 39632093 PMC: 11622171. DOI: 10.1523/JNEUROSCI.1357-24.2024.


The Role of Acid-Sensing Ion Channel 1A (ASIC1A) in the Behavioral and Synaptic Effects of Oxycodone and Other Opioids.

Fuller M, Andrys N, Gupta S, Ghobbeh A, Kreple C, Fan R Int J Mol Sci. 2024; 25(21).

PMID: 39519136 PMC: 11545886. DOI: 10.3390/ijms252111584.


Association of Neuromelanin-Sensitive MRI Signal With Lifetime Substance Use in Young Women.

Perlman G, Wengler K, Moeller S, Kotov R, Klein D, Weinstein J Am J Psychiatry. 2024; 181(11):997-1005.

PMID: 39380373 PMC: 11637462. DOI: 10.1176/appi.ajp.20220819.


Targeting Neuroplasticity in Substance Use Disorders: Implications for Therapeutics.

Wolf M Annu Rev Pharmacol Toxicol. 2024; 65(1):259-280.

PMID: 39374445 PMC: 11864087. DOI: 10.1146/annurev-pharmtox-061724-080548.


References
1.
Quinlan E, Philpot B, Huganir R, Bear M . Rapid, experience-dependent expression of synaptic NMDA receptors in visual cortex in vivo. Nat Neurosci. 1999; 2(4):352-7. DOI: 10.1038/7263. View

2.
Churchill L, Swanson C, Urbina M, Kalivas P . Repeated cocaine alters glutamate receptor subunit levels in the nucleus accumbens and ventral tegmental area of rats that develop behavioral sensitization. J Neurochem. 1999; 72(6):2397-403. DOI: 10.1046/j.1471-4159.1999.0722397.x. View

3.
Kelz M, Chen J, Carlezon Jr W, Whisler K, GILDEN L, Beckmann A . Expression of the transcription factor deltaFosB in the brain controls sensitivity to cocaine. Nature. 1999; 401(6750):272-6. DOI: 10.1038/45790. View

4.
Quinlan E, Olstein D, Bear M . Bidirectional, experience-dependent regulation of N-methyl-D-aspartate receptor subunit composition in the rat visual cortex during postnatal development. Proc Natl Acad Sci U S A. 1999; 96(22):12876-80. PMC: 23143. DOI: 10.1073/pnas.96.22.12876. View

5.
Carroll R, Beattie E, Xia H, Luscher C, Altschuler Y, Nicoll R . Dynamin-dependent endocytosis of ionotropic glutamate receptors. Proc Natl Acad Sci U S A. 1999; 96(24):14112-7. PMC: 24199. DOI: 10.1073/pnas.96.24.14112. View