Elevation of Transient Receptor Potential Vanilloid 1 Function in the Lateral Habenula Mediates Aversive Behaviors in Alcohol-withdrawn Rats

WHAT WE ALREADY KNOW ABOUT THIS TOPICChronic alcohol use and withdrawal leads to increased pain perception, anxiety, and depression. These aberrant behaviors are accompanied by increased excitatory glutamatergic transmission to, and activity of, the lateral habenula neurons.Vanilloid type 1, or TRPV...

Full description

Saved in:
Bibliographic Details
Published in:Anesthesiology (Philadelphia) 2019-04, Vol.130 (4), p.592-608
Main Authors: Gregor, Danielle M, Zuo, Wanhong, Fu, Rao, Bekker, Alex, Ye, Jiang-Hong
Format: Article
Language:English
Subjects:
Alcoholism - complications
Alcoholism - drug therapy
Alcoholism - metabolism
Animals
Avoidance Learning - drug effects
Avoidance Learning - physiology
Dopamine - analogs & derivatives
Dopamine - pharmacology
Dopamine - therapeutic use
Ethanol - administration & dosage
Habenula - drug effects
Habenula - metabolism
Male
Organ Culture Techniques
Rats
Rats, Long-Evans
Substance Withdrawal Syndrome - drug therapy
Substance Withdrawal Syndrome - etiology
Substance Withdrawal Syndrome - metabolism
TRPV Cation Channels - antagonists & inhibitors
TRPV Cation Channels - biosynthesis
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:WHAT WE ALREADY KNOW ABOUT THIS TOPICChronic alcohol use and withdrawal leads to increased pain perception, anxiety, and depression. These aberrant behaviors are accompanied by increased excitatory glutamatergic transmission to, and activity of, the lateral habenula neurons.Vanilloid type 1, or TRPV1, channels are expressed in the habenula and they facilitate glutamatergic transmission. Whether TRPV1 channel plays a role in habenula hyperactivity is not clear. WHAT THIS ARTICLE TELLS US THAT IS NEWGlutamatergic transmission in the lateral habenula was inhibited by TRPV1 channel antagonists. In vivo, local administration of TRPV1 antagonists into the lateral habenula attenuated hyperalgesia, anxiety, and relapse-like drinking in rats who chronically consumed alcohol.The data suggest that enhanced TRPV1 channel function during withdrawal may contribute to aberrant behavior that promotes relapse alcohol consumption. BACKGROUND:Recent rat studies indicate that alcohol withdrawal can trigger a negative emotional state including anxiety- and depression-like behaviors and hyperalgesia, as well as elevated glutamatergic transmission and activity in lateral habenula neurons. TRPV1, a vanilloid receptor expressed in the habenula, is involved in pain, alcohol dependence, and glutamatergic transmission. The authors therefore hypothesized that TRPV1 contributes to the changes in both the behavioral phenotypes and the habenula activity in alcohol-withdrawn rats. METHODS:Adult male Long-Evans rats (n = 110 and 280 for electrophysiology and behaviors, respectively), randomly assigned into the alcohol and water (Naïve) groups, were trained to consume either alcohol or water-only using an intermittent-access procedure. Slice electrophysiology was used to measure spontaneous excitatory postsynaptic currents and firing of lateral habenula neurons. The primary outcome was the change in alcohol-related behaviors and lateral habenula activity induced by pharmacologic manipulation of TRPV1 activity. RESULTS:The basal frequency of spontaneous excitatory postsynaptic currents and firing of lateral habenula neurons in alcohol-withdrawn rats was significantly increased. The TRPV1 antagonist capsazepine (10 µM) induced a stronger inhibition on spontaneous excitatory postsynaptic currents (mean ± SD; by 26.1 ± 27.9% [n = 11] vs. 6.7 ± 18.6% [n = 17], P = 0.027) and firing (by 23.4 ± 17.6% [n = 9] vs. 11.9 ± 16.3% [n = 12], P = 0.025) in Withdrawn rats than Naive rats. By contrast, the
ISSN:0003-3022
1528-1175
DOI:10.1097/ALN.0000000000002615