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Synaptic adaptations in the central amygdala and hypothalamic paraventricular nucleus associated with protracted ethanol abstinence in male rhesus monkeys.
Neuropsychopharmacology. 2019 04; 44(5):982-993.N

Abstract

Alcohol use disorder is a significant global burden. Stress has been identified as an etiological factor in the initiation and continuation of ethanol consumption. Understanding adaptations within stress circuitry is an important step toward novel treatment strategies. The effects of protracted abstinence following long-term ethanol self-administration on the central nucleus of the amygdala (CeA) and the hypothalamic paraventricular nucleus (PVN) were evaluated in male rhesus monkeys. Using whole-cell patch-clamp electrophysiology, inhibitory GABAergic transmission in the CeA and excitatory glutamatergic transmission in the PVN were measured. CeA neurons from abstinent drinkers displayed an elevated baseline spontaneous inhibitory postsynaptic current (sIPSC) frequency compared with controls, indicating increased presynaptic GABA release. Application of acute ethanol significantly increased the frequency of sIPSCs in controls, but not in abstinent drinkers, suggesting a tolerance to ethanol-enhanced GABA release in abstinent rhesus monkeys with a history of chronic ethanol self-administration and repeated abstinence. In the PVN, the frequency of spontaneous excitatory postsynaptic currents (sEPSC) was elevated in abstinent drinkers compared with controls, indicating increased presynaptic glutamate release. Notably, acute ethanol decreased presynaptic glutamate release onto parvocellular PVN neurons in both controls and abstinent drinkers, suggesting a lack of tolerance to acute ethanol among PVN neurons. These results are the first to demonstrate distinct synaptic adaptations and ethanol sensitivity in both the extrahypothalamic and hypothalamic stress circuits in abstinent rhesus males. Importantly, our findings describe adaptations in stress circuitry present in the brain at a state during abstinence, just prior to relapse to ethanol drinking.

Authors+Show Affiliations

Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA. Division of Neuroscience, Oregon National Primate Research Center, Portland, OR, USA.Bowles Center for Alcohol Studies and Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, 92037, USA.Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA. Division of Neuroscience, Oregon National Primate Research Center, Portland, OR, USA.Division of Neuroscience, Oregon National Primate Research Center, Portland, OR, USA.Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA. grantka@ohsu.edu. Division of Neuroscience, Oregon National Primate Research Center, Portland, OR, USA. grantka@ohsu.edu.Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, 92037, USA. mroberto@scripps.edu.

Pub Type(s)

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

Language

eng

PubMed ID

30555160

Citation

Jimenez, V A., et al. "Synaptic Adaptations in the Central Amygdala and Hypothalamic Paraventricular Nucleus Associated With Protracted Ethanol Abstinence in Male Rhesus Monkeys." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 44, no. 5, 2019, pp. 982-993.
Jimenez VA, Herman MA, Cuzon Carlson VC, et al. Synaptic adaptations in the central amygdala and hypothalamic paraventricular nucleus associated with protracted ethanol abstinence in male rhesus monkeys. Neuropsychopharmacology. 2019;44(5):982-993.
Jimenez, V. A., Herman, M. A., Cuzon Carlson, V. C., Walter, N. A., Grant, K. A., & Roberto, M. (2019). Synaptic adaptations in the central amygdala and hypothalamic paraventricular nucleus associated with protracted ethanol abstinence in male rhesus monkeys. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 44(5), 982-993. https://doi.org/10.1038/s41386-018-0290-7
Jimenez VA, et al. Synaptic Adaptations in the Central Amygdala and Hypothalamic Paraventricular Nucleus Associated With Protracted Ethanol Abstinence in Male Rhesus Monkeys. Neuropsychopharmacology. 2019;44(5):982-993. PubMed PMID: 30555160.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synaptic adaptations in the central amygdala and hypothalamic paraventricular nucleus associated with protracted ethanol abstinence in male rhesus monkeys. AU - Jimenez,V A, AU - Herman,M A, AU - Cuzon Carlson,V C, AU - Walter,N A, AU - Grant,K A, AU - Roberto,M, Y1 - 2018/12/05/ PY - 2018/08/07/received PY - 2018/11/27/accepted PY - 2018/11/25/revised PY - 2018/12/18/pubmed PY - 2019/12/19/medline PY - 2018/12/18/entrez SP - 982 EP - 993 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 44 IS - 5 N2 - Alcohol use disorder is a significant global burden. Stress has been identified as an etiological factor in the initiation and continuation of ethanol consumption. Understanding adaptations within stress circuitry is an important step toward novel treatment strategies. The effects of protracted abstinence following long-term ethanol self-administration on the central nucleus of the amygdala (CeA) and the hypothalamic paraventricular nucleus (PVN) were evaluated in male rhesus monkeys. Using whole-cell patch-clamp electrophysiology, inhibitory GABAergic transmission in the CeA and excitatory glutamatergic transmission in the PVN were measured. CeA neurons from abstinent drinkers displayed an elevated baseline spontaneous inhibitory postsynaptic current (sIPSC) frequency compared with controls, indicating increased presynaptic GABA release. Application of acute ethanol significantly increased the frequency of sIPSCs in controls, but not in abstinent drinkers, suggesting a tolerance to ethanol-enhanced GABA release in abstinent rhesus monkeys with a history of chronic ethanol self-administration and repeated abstinence. In the PVN, the frequency of spontaneous excitatory postsynaptic currents (sEPSC) was elevated in abstinent drinkers compared with controls, indicating increased presynaptic glutamate release. Notably, acute ethanol decreased presynaptic glutamate release onto parvocellular PVN neurons in both controls and abstinent drinkers, suggesting a lack of tolerance to acute ethanol among PVN neurons. These results are the first to demonstrate distinct synaptic adaptations and ethanol sensitivity in both the extrahypothalamic and hypothalamic stress circuits in abstinent rhesus males. Importantly, our findings describe adaptations in stress circuitry present in the brain at a state during abstinence, just prior to relapse to ethanol drinking. SN - 1740-634X UR - https://www.unboundmedicine.com/medline/citation/30555160/Synaptic_adaptations_in_the_central_amygdala_and_hypothalamic_paraventricular_nucleus_associated_with_protracted_ethanol_abstinence_in_male_rhesus_monkeys_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/30555160/ DB - PRIME DP - Unbound Medicine ER -