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CRF modulates glutamate transmission in the central amygdala of naïve and ethanol-dependent rats.
Neuropharmacology 2017; 125:418-428N

Abstract

Corticotropin-releasing factor (CRF) signaling in the central nucleus of the amygdala (CeA) is hypothesized to drive the development of alcohol dependence, as it regulates ethanol intake and several anxiogenic behaviors linked to withdrawal. Excitatory glutamatergic neurotransmission contributes to alcohol reinforcement, tolerance and dependence. Therefore, in this study we used in vitro slice electrophysiology to investigate the effects of CRF and its receptor subtype (CRF1 and CRF2) antagonists on both evoked and spontaneous action potential-independent glutamatergic transmission in the CeA of naive and ethanol-dependent Sprague-Dawley rats. We found that CRF (25-200 nM) concentration-dependently diminished evoked compound excitatory postsynaptic potentials (EPSPs), but increased miniature excitatory postsynaptic current (mEPSC) frequencies similarly in CeA neurons of both naïve and ethanol-dependent rats, indicating reduced evoked glutamatergic responses and enhanced vesicular glutamate release, respectively. This CRF-induced vesicular glutamate release was prevented by the CRF1/2 antagonist (Astressin B) and the CRF1 antagonist (R121919), but not by the CRF2 antagonist (Astressin 2B). Similarly, CRF's effects on evoked glutamatergic responses were completely blocked by CRF1 antagonism, but only slightly decreased in the presence of the CRF2 antagonist. Moreover, CRF1 antagonism reveals a tonic facilitation of vesicular glutamate, whereas the CRF2 antagonism revealed a tonic inhibition of vesicular glutamate release. Collectively our data show that CRF primarily acts at presynaptic CRF1 to produce opposite effects on CeA evoked and spontaneous glutamate release and that the CRF system modulates CeA glutamatergic synapses throughout the development of alcohol dependence.

Authors+Show Affiliations

Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA.Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA; Department of Pharmacology, Universidade Federal do Paraná, Jardim das Américas, Curitiba, Paraná, CEP 81531-990, Brazil.Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA.Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA.Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA.Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA.Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA.Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA. Electronic address: mroberto@scripps.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28807676

Citation

Varodayan, Florence P., et al. "CRF Modulates Glutamate Transmission in the Central Amygdala of Naïve and Ethanol-dependent Rats." Neuropharmacology, vol. 125, 2017, pp. 418-428.
Varodayan FP, Correia D, Kirson D, et al. CRF modulates glutamate transmission in the central amygdala of naïve and ethanol-dependent rats. Neuropharmacology. 2017;125:418-428.
Varodayan, F. P., Correia, D., Kirson, D., Khom, S., Oleata, C. S., Luu, G., ... Roberto, M. (2017). CRF modulates glutamate transmission in the central amygdala of naïve and ethanol-dependent rats. Neuropharmacology, 125, pp. 418-428. doi:10.1016/j.neuropharm.2017.08.009.
Varodayan FP, et al. CRF Modulates Glutamate Transmission in the Central Amygdala of Naïve and Ethanol-dependent Rats. Neuropharmacology. 2017;125:418-428. PubMed PMID: 28807676.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CRF modulates glutamate transmission in the central amygdala of naïve and ethanol-dependent rats. AU - Varodayan,Florence P, AU - Correia,Diego, AU - Kirson,Dean, AU - Khom,Sophia, AU - Oleata,Christopher S, AU - Luu,George, AU - Schweitzer,Paul, AU - Roberto,Marisa, Y1 - 2017/08/12/ PY - 2017/04/26/received PY - 2017/07/21/revised PY - 2017/08/09/accepted PY - 2017/8/16/pubmed PY - 2018/6/13/medline PY - 2017/8/16/entrez KW - Alcohol/ethanol KW - Amygdala KW - CRF KW - CRF receptor KW - Electrophysiology KW - Glutamate SP - 418 EP - 428 JF - Neuropharmacology JO - Neuropharmacology VL - 125 N2 - Corticotropin-releasing factor (CRF) signaling in the central nucleus of the amygdala (CeA) is hypothesized to drive the development of alcohol dependence, as it regulates ethanol intake and several anxiogenic behaviors linked to withdrawal. Excitatory glutamatergic neurotransmission contributes to alcohol reinforcement, tolerance and dependence. Therefore, in this study we used in vitro slice electrophysiology to investigate the effects of CRF and its receptor subtype (CRF1 and CRF2) antagonists on both evoked and spontaneous action potential-independent glutamatergic transmission in the CeA of naive and ethanol-dependent Sprague-Dawley rats. We found that CRF (25-200 nM) concentration-dependently diminished evoked compound excitatory postsynaptic potentials (EPSPs), but increased miniature excitatory postsynaptic current (mEPSC) frequencies similarly in CeA neurons of both naïve and ethanol-dependent rats, indicating reduced evoked glutamatergic responses and enhanced vesicular glutamate release, respectively. This CRF-induced vesicular glutamate release was prevented by the CRF1/2 antagonist (Astressin B) and the CRF1 antagonist (R121919), but not by the CRF2 antagonist (Astressin 2B). Similarly, CRF's effects on evoked glutamatergic responses were completely blocked by CRF1 antagonism, but only slightly decreased in the presence of the CRF2 antagonist. Moreover, CRF1 antagonism reveals a tonic facilitation of vesicular glutamate, whereas the CRF2 antagonism revealed a tonic inhibition of vesicular glutamate release. Collectively our data show that CRF primarily acts at presynaptic CRF1 to produce opposite effects on CeA evoked and spontaneous glutamate release and that the CRF system modulates CeA glutamatergic synapses throughout the development of alcohol dependence. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/28807676/CRF_modulates_glutamate_transmission_in_the_central_amygdala_of_naïve_and_ethanol_dependent_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(17)30376-3 DB - PRIME DP - Unbound Medicine ER -