CRF modulates glutamate transmission in the central amygdala of naïve and ethanol-dependent rats

Autor: Florence P. Varodayan, George Luu, Christopher S. Oleata, Dean Kirson, Diego Correia, Paul Schweitzer, Sophia Khom, Marisa Roberto
Rok vydání: 2017
Předmět:
0301 basic medicine
Male
medicine.medical_specialty
Corticotropin-Releasing Hormone
Glutamic Acid
Biology
Neurotransmission
Receptors
Corticotropin-Releasing Hormone
Synaptic Transmission
Article
Rats
Sprague-Dawley
Tissue Culture Techniques
03 medical and health sciences
Cellular and Molecular Neuroscience
Glutamatergic
chemistry.chemical_compound
0302 clinical medicine
Astressin-B
Internal medicine
medicine
DNQX
Animals
Pharmacology
Neurotransmitter Agents
Ethanol
Central nucleus of the amygdala
Central Amygdaloid Nucleus
Antagonist
Glutamate receptor
Central Nervous System Depressants
Alcoholism
Disease Models
Animal
030104 developmental biology
Endocrinology
chemistry
Synapses
Excitatory postsynaptic potential
030217 neurology & neurosurgery
hormones
hormone substitutes
and hormone antagonists
Zdroj: Neuropharmacology. 125
ISSN: 1873-7064
Popis: 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 naive 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.
Databáze: OpenAIRE
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