Cited by 53Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchNicotinic Acetylcholine Receptors Study

Temporally Dependent Changes in Cocaine-Induced Synaptic Plasticity in the Nucleus Accumbens Shell are Reversed by D1-Like Dopamine Receptor Stimulation

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Ortinski, Pavel I, Vassoler, Fair M, Carlson, Gregory C, Pierce, R Christopher·2012·Neuropsychopharmacology

Abstract

Dopaminergic and glutamatergic inputs to the nucleus accumbens shell have a central role in reward processing. Non-contingent cocaine administration generates a number of long-term AMPA receptor-dependent changes in synaptic efficacy. However, the synaptic consequences of cocaine self-administration and the potential role of dopamine in these processes remain unclear. Here, we examined the influence of D1 dopamine receptor (D1DR) activation on excitatory synaptic plasticity in the accumbens shell of adult rats following cocaine self-administration. Our results indicated that during the first 2 days following cocaine exposure both pre- and post-synaptic mechanisms contribute to a net decrease in AMPA receptor-mediated signaling. This is reflected by decreased frequency of miniature EPSCs (mEPSCs) attributable to enhanced cannabinoid receptor activity, decreased mEPSC amplitude, and increased paired-pulse ratio of evoked EPSCs. In contrast, the only changes observed in the shell 3-4 weeks following cocaine self-administration were increased mEPSCs amplitudes and AMPA/NMDA ratios. We further found that although these cocaine-induced neuroadaptations during early and late abstinence have different synaptic expression mechanisms, they were normalized by stimulation of D1DRs. Thus, pre-exposure to the D1DR agonist, SKF38393, during the initial period of abstinence increased excitatory synaptic strength, but reduced excitatory signaling after weeks of abstinence. Taken together, these results indicate that the direction of changes in excitatory transmission induced by cocaine self-administration switches over the first few weeks of abstinence. Moreover, D1DRs gate the stability of these cocaine-induced changes at glutamatergic synapses in the accumbens shell by utilizing multiple temporally distinct mechanisms, which has implications for the treatment of cocaine craving and addiction.

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Authors
Ortinski, P. I., Vassoler, F. M., Carlson, G. C., & Pierce, R. C.
Affiliations
University of Pennsylvania (US)
Corresponding author
Ortinski, Pavel I
Venue
Neuropsychopharmacology
Published
2012-03-14
Volume
37
Issue
7
Pages
1671-1682
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
OpenAlex
W2054667632
Cited by
53
References
63
Citations by year
2026: 1 · 2024: 1 · 2023: 5 · 2022: 4 · 2021: 3 · 2020: 2 · 2019: 3 · 2018: 7 · 2017: 4 · 2016: 4 · 2015: 3 · 2014: 3 · 2013: 10 · 2012: 3
FWCI
2.50
Type
journal article
Language
en
Open access
Locations
  • Neuropsychopharmacology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute on Drug Abuse (K02 DA18678, R01DA022339, K01DA031747, R01 DA22339, K02DA018678)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Keywords
cocaine self-administration, nucleus accumbens shell, dopamine D1 receptor, synaptic plasticity, AMPA receptors, miniature EPSCs, cannabinoid receptors, paired-pulse ratio, cocaine abstinence, cocaine craving, cocaine dependence, glutamatergic synapses, reward processing
MeSH terms
Animals, Cocaine, Male, Microinjections, Synaptic Transmission, Neuronal Plasticity, Nucleus Accumbens, Self Administration, Synapses, 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Receptors, Dopamine D1, Receptors, AMPA, Dopamine Agonists, Dopamine Uptake Inhibitors, Excitatory Postsynaptic Potentials, Rats, Miniature Postsynaptic Potentials

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