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Chronic cocaine enhances corticotropin-releasing factor-dependent potentiation of excitatory transmission in ventral tegmental area dopamine neurons.
J Neurosci 2009; 29(20):6535-44JN

Abstract

Current concepts suggest that stress-induced release of neuromodulators such as corticotropin-releasing factor (CRF) can drive drug-dependent behaviors. Although previous drug exposure can enhance behavioral and neurochemical responses to stress, it is unclear how such drug exposure alters the CRF modulation of excitatory synapses onto ventral tegmental area (VTA) dopamine neurons, a key locus of drug- and stress-induced neuroadaptation. Here, we demonstrate that, after repeated cocaine exposure, the magnitude and duration of the CRF-induced potentiation of NMDA receptor (NMDAR)-mediated neurotransmission was significantly increased compared with naive and saline-treated mice. Furthermore, CRF enhanced AMPA receptor (AMPAR)-mediated transmission only in mice that were exposed to cocaine. Increased frequency of AMPAR-mediated spontaneous miniature EPSCs and the intracellular blockade of CRF potentiation of AMPAR-mediated transmission suggest both presynaptic and postsynaptic effects of CRF. Importantly, pharmacological experiments revealed that CRF receptor 1 and protein kinase A pathways were newly recruited after repeated cocaine for the enhancement of CRF-induced NMDAR potentiation and the appearance of AMPAR potentiation. Thus, enhanced CRF-induced potentiation of excitatory synaptic transmission onto VTA dopamine neurons after cocaine preexposure is likely to produce an abnormal increase in dopamine release during stressful events and could augment activation of addictive behaviors in response to stress.

Authors+Show Affiliations

Ernest Gallo Clinic and Research Center, Emeryville, California 94608, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19458224

Citation

Hahn, Junghyun, et al. "Chronic Cocaine Enhances Corticotropin-releasing Factor-dependent Potentiation of Excitatory Transmission in Ventral Tegmental Area Dopamine Neurons." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 29, no. 20, 2009, pp. 6535-44.
Hahn J, Hopf FW, Bonci A. Chronic cocaine enhances corticotropin-releasing factor-dependent potentiation of excitatory transmission in ventral tegmental area dopamine neurons. J Neurosci. 2009;29(20):6535-44.
Hahn, J., Hopf, F. W., & Bonci, A. (2009). Chronic cocaine enhances corticotropin-releasing factor-dependent potentiation of excitatory transmission in ventral tegmental area dopamine neurons. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 29(20), pp. 6535-44. doi:10.1523/JNEUROSCI.4773-08.2009.
Hahn J, Hopf FW, Bonci A. Chronic Cocaine Enhances Corticotropin-releasing Factor-dependent Potentiation of Excitatory Transmission in Ventral Tegmental Area Dopamine Neurons. J Neurosci. 2009 May 20;29(20):6535-44. PubMed PMID: 19458224.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chronic cocaine enhances corticotropin-releasing factor-dependent potentiation of excitatory transmission in ventral tegmental area dopamine neurons. AU - Hahn,Junghyun, AU - Hopf,F Woodward, AU - Bonci,Antonello, PY - 2009/5/22/entrez PY - 2009/5/22/pubmed PY - 2009/6/9/medline SP - 6535 EP - 44 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J. Neurosci. VL - 29 IS - 20 N2 - Current concepts suggest that stress-induced release of neuromodulators such as corticotropin-releasing factor (CRF) can drive drug-dependent behaviors. Although previous drug exposure can enhance behavioral and neurochemical responses to stress, it is unclear how such drug exposure alters the CRF modulation of excitatory synapses onto ventral tegmental area (VTA) dopamine neurons, a key locus of drug- and stress-induced neuroadaptation. Here, we demonstrate that, after repeated cocaine exposure, the magnitude and duration of the CRF-induced potentiation of NMDA receptor (NMDAR)-mediated neurotransmission was significantly increased compared with naive and saline-treated mice. Furthermore, CRF enhanced AMPA receptor (AMPAR)-mediated transmission only in mice that were exposed to cocaine. Increased frequency of AMPAR-mediated spontaneous miniature EPSCs and the intracellular blockade of CRF potentiation of AMPAR-mediated transmission suggest both presynaptic and postsynaptic effects of CRF. Importantly, pharmacological experiments revealed that CRF receptor 1 and protein kinase A pathways were newly recruited after repeated cocaine for the enhancement of CRF-induced NMDAR potentiation and the appearance of AMPAR potentiation. Thus, enhanced CRF-induced potentiation of excitatory synaptic transmission onto VTA dopamine neurons after cocaine preexposure is likely to produce an abnormal increase in dopamine release during stressful events and could augment activation of addictive behaviors in response to stress. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/19458224/Chronic_cocaine_enhances_corticotropin_releasing_factor_dependent_potentiation_of_excitatory_transmission_in_ventral_tegmental_area_dopamine_neurons_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=19458224 DB - PRIME DP - Unbound Medicine ER -