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Prelimbic cortex and ventral tegmental area modulate synaptic plasticity differentially in nucleus accumbens during cocaine-reinstated drug seeking.
Neuropsychopharmacology 2014; 39(5):1169-77N

Abstract

Addictive drug use causes long-lasting changes in synaptic strength and dendritic spine morphology in the nucleus accumbens that might underlie the vulnerability to relapse. Although activity in mesocorticolimbic circuitry is required for reinstating cocaine seeking, its role in reinstatement-associated synaptic plasticity is not well characterized. Using rats extinguished from cocaine self-administration, we found potentiated synaptic strength (assessed as the AMPA/NMDA current amplitude ratio) and increased spine head diameter in medium spiny neurons in the accumbens core (NAcore). The basal changes in synaptic strength and morphology in cocaine-extinguished animals were further augmented during cocaine-induced reinstatement. Two NAcore afferents contributing to cocaine reinstatement are glutamatergic inputs from the prelimbic prefrontal cortex (PL) and dopamine from the ventral tegmental area (VTA). Pharmacological inhibition of either PL or VTA prevented cocaine-primed reinstatement. However, inhibiting the PL further potentiated AMPA/NMDA and spine head diameter, while inactivating the VTA or the combined systemic administration of dopamine D1 and D2 antagonists prevented the increase in AMPA/NMDA and spine diameter induced by cocaine priming. These data indicate that neuronal activity in the VTA and associated dopamine receptor stimulation is necessary for the synaptic potentiation in the NAcore during cocaine-induced reinstatement. Although activity in the PL was necessary for reinstatement, it inhibited synaptic potentiation initiated by an acute cocaine injection. Thus, although the PL and VTA differentially regulate the direction of synaptic plasticity induced by a cocaine-priming injection, coordinated synaptic potentiation by both NAcore afferents is necessary for cocaine-induced relapse.

Authors+Show Affiliations

1] Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA [2] National Institute on Drug Dependence, Peking University, Beijing, People's Republic of China.Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.Department of Neuroscience, Vrije University of Amsterdam, Amsterdam, The Netherlands.Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24232172

Citation

Shen, Hao-wei, et al. "Prelimbic Cortex and Ventral Tegmental Area Modulate Synaptic Plasticity Differentially in Nucleus Accumbens During Cocaine-reinstated Drug Seeking." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 39, no. 5, 2014, pp. 1169-77.
Shen HW, Gipson CD, Huits M, et al. Prelimbic cortex and ventral tegmental area modulate synaptic plasticity differentially in nucleus accumbens during cocaine-reinstated drug seeking. Neuropsychopharmacology. 2014;39(5):1169-77.
Shen, H. W., Gipson, C. D., Huits, M., & Kalivas, P. W. (2014). Prelimbic cortex and ventral tegmental area modulate synaptic plasticity differentially in nucleus accumbens during cocaine-reinstated drug seeking. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 39(5), pp. 1169-77. doi:10.1038/npp.2013.318.
Shen HW, et al. Prelimbic Cortex and Ventral Tegmental Area Modulate Synaptic Plasticity Differentially in Nucleus Accumbens During Cocaine-reinstated Drug Seeking. Neuropsychopharmacology. 2014;39(5):1169-77. PubMed PMID: 24232172.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prelimbic cortex and ventral tegmental area modulate synaptic plasticity differentially in nucleus accumbens during cocaine-reinstated drug seeking. AU - Shen,Hao-wei, AU - Gipson,Cassandra D, AU - Huits,Martijn, AU - Kalivas,Peter W, Y1 - 2013/11/15/ PY - 2013/08/05/received PY - 2013/10/10/revised PY - 2013/10/16/accepted PY - 2013/11/16/entrez PY - 2013/11/16/pubmed PY - 2014/12/15/medline SP - 1169 EP - 77 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 39 IS - 5 N2 - Addictive drug use causes long-lasting changes in synaptic strength and dendritic spine morphology in the nucleus accumbens that might underlie the vulnerability to relapse. Although activity in mesocorticolimbic circuitry is required for reinstating cocaine seeking, its role in reinstatement-associated synaptic plasticity is not well characterized. Using rats extinguished from cocaine self-administration, we found potentiated synaptic strength (assessed as the AMPA/NMDA current amplitude ratio) and increased spine head diameter in medium spiny neurons in the accumbens core (NAcore). The basal changes in synaptic strength and morphology in cocaine-extinguished animals were further augmented during cocaine-induced reinstatement. Two NAcore afferents contributing to cocaine reinstatement are glutamatergic inputs from the prelimbic prefrontal cortex (PL) and dopamine from the ventral tegmental area (VTA). Pharmacological inhibition of either PL or VTA prevented cocaine-primed reinstatement. However, inhibiting the PL further potentiated AMPA/NMDA and spine head diameter, while inactivating the VTA or the combined systemic administration of dopamine D1 and D2 antagonists prevented the increase in AMPA/NMDA and spine diameter induced by cocaine priming. These data indicate that neuronal activity in the VTA and associated dopamine receptor stimulation is necessary for the synaptic potentiation in the NAcore during cocaine-induced reinstatement. Although activity in the PL was necessary for reinstatement, it inhibited synaptic potentiation initiated by an acute cocaine injection. Thus, although the PL and VTA differentially regulate the direction of synaptic plasticity induced by a cocaine-priming injection, coordinated synaptic potentiation by both NAcore afferents is necessary for cocaine-induced relapse. SN - 1740-634X UR - https://www.unboundmedicine.com/medline/citation/24232172/Prelimbic_cortex_and_ventral_tegmental_area_modulate_synaptic_plasticity_differentially_in_nucleus_accumbens_during_cocaine_reinstated_drug_seeking_ L2 - http://dx.doi.org/10.1038/npp.2013.318 DB - PRIME DP - Unbound Medicine ER -