Premium
Ethanol metabolite increases activity of CeA neurons and requires activation of local NMDA receptors (1125.5)
Author(s) -
Chapp Andrew,
Larson Robert,
Huber Michael,
Carter Jason,
Chen QingHui
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1125.5
Subject(s) - rostral ventrolateral medulla , chemistry , nmda receptor , medulla oblongata , medicine , endocrinology , glutamate receptor , receptor , central nervous system , biochemistry
The central nucleus of amygdala (CeA) is involved in the sympathoexcitatory and pressor responses to ethanol intake. However, the underlying neural mechanisms have not been determined. Here we investigated the role of acetate, the ethanol metabolite, in regulating the in vitro excitability of CeA neurons with axon projecting to rostral ventrolateral medulla (CeA‐RVLM) under brain slice preparation. In current‐clamp recordings, graded current injections evoked graded increases in spike frequency. Maximum discharge was evoked by +250 pA injections and averaged 18 ± 1 Hz (n=7). Bath application of acetate (0, 7.5, 37.5 and 75 mM) increased the excitability of CeA‐RVLM neurons in a dose‐dependent manner. Maximum spike discharge in the presence of acetate (75 mM) was 53 ± 3 Hz (n=4), which was significantly (p<0.01) higher than vehicle control. Pre‐treatment with AP5 (60 µM, n=7), the NMDA receptor blocker, significantly prevented increase in excitability (37 ± 5 Hz, p<0.05) elicited by acetate. AP5 alone was without effect on baseline excitability. The contribution of acetate in regulating sympathetic nerve activity (SNA) was assessed by microinjecting acetate into the CeA of anesthetized rat. Acetate (0.2 µmol/100 nl) significantly (P<0.05) increased lumber SNA by 90 ± 1 %, splanchnic SNA by 76 ± 18% and MAP by 4 ± 1 mmHg (n=3). Immunohistochemistry study demonstrates expression of NMDA NR1 in CeA‐RVLM neurons. Our data indicate that activation of NMDA receptors by acetate contributes to the increased excitability of CeA‐RVLM neurons. The CeA acetate elicited sympathoexcitatory responses involve the activation of CeA‐RVLM neurons, which may underlie the mechanisms of increased SNA during the development of alcohol associated hypertension. Grant Funding Source : Supported by AHA 10SDG2640130