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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of Transient Receptor Potential Vanilloid 1 Function in the Lateral Habenula Mediates Aversive Behaviors in Alcohol-withdrawn Rats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...
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| Published in: | Anesthesiology (Philadelphia) 2019-04, Vol.130 (4), p.592-608 |
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| description | 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that TRPV1 contributes to the changes in both the behavioral phenotypes and the habenula activity in alcohol-withdrawn rats.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 |
| doi_str_mv | 10.1097/ALN.0000000000002615 |
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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 TRPV1 agonist capsaicin (3 μM) produced a weaker potentiation in Withdrawn than Naïve rats (spontaneous excitatory postsynaptic currentsby 203.6 ± 124.7% [n = 20] vs. 415.2 ± 424.3% [n = 15], P < 0.001; firing38.1 ± 14.7% [n = 11] vs. 73.9 ± 41.9% [n = 11], P < 0.001). Conversely, capsaicin’s actions in Naïve but not in Withdrawn rats were significantly attenuated by the pretreatment of TRPV1 endogenous agonist N-Oleoyldopamine. In Withdrawn rats, intra-habenula infusion of TRPV1 antagonists attenuated hyperalgesia and anxiety-like behaviors, decreased alcohol consumption upon resuming drinking, and elicited a conditioned place preference.
CONCLUSIONS:Enhanced TRPV1 function may contribute to increased glutamatergic transmission and activity of lateral habenula neurons, resulting in the aberrant behaviors during ethanol withdrawal.</description><identifier>ISSN: 0003-3022</identifier><identifier>EISSN: 1528-1175</identifier><identifier>DOI: 10.1097/ALN.0000000000002615</identifier><identifier>PMID: 30676422</identifier><language>eng</language><publisher>United States: Copyright by , the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc</publisher><subject>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</subject><ispartof>Anesthesiology (Philadelphia), 2019-04, Vol.130 (4), p.592-608</ispartof><rights>Copyright © by 2019, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4835-9d626f2965b3d92a844eadb289cdacd6fe9a6d3677bd394b7b63284434f836a43</citedby><cites>FETCH-LOGICAL-c4835-9d626f2965b3d92a844eadb289cdacd6fe9a6d3677bd394b7b63284434f836a43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,786,790,891,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30676422$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gregor, Danielle M</creatorcontrib><creatorcontrib>Zuo, Wanhong</creatorcontrib><creatorcontrib>Fu, Rao</creatorcontrib><creatorcontrib>Bekker, Alex</creatorcontrib><creatorcontrib>Ye, Jiang-Hong</creatorcontrib><title>Elevation of Transient Receptor Potential Vanilloid 1 Function in the Lateral Habenula Mediates Aversive Behaviors in Alcohol-withdrawn Rats</title><title>Anesthesiology (Philadelphia)</title><addtitle>Anesthesiology</addtitle><description>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 TRPV1 agonist capsaicin (3 μM) produced a weaker potentiation in Withdrawn than Naïve rats (spontaneous excitatory postsynaptic currentsby 203.6 ± 124.7% [n = 20] vs. 415.2 ± 424.3% [n = 15], P < 0.001; firing38.1 ± 14.7% [n = 11] vs. 73.9 ± 41.9% [n = 11], P < 0.001). Conversely, capsaicin’s actions in Naïve but not in Withdrawn rats were significantly attenuated by the pretreatment of TRPV1 endogenous agonist N-Oleoyldopamine. In Withdrawn rats, intra-habenula infusion of TRPV1 antagonists attenuated hyperalgesia and anxiety-like behaviors, decreased alcohol consumption upon resuming drinking, and elicited a conditioned place preference.
CONCLUSIONS:Enhanced TRPV1 function may contribute to increased glutamatergic transmission and activity of lateral habenula neurons, resulting in the aberrant behaviors during ethanol withdrawal.</description><subject>Alcoholism - complications</subject><subject>Alcoholism - drug therapy</subject><subject>Alcoholism - metabolism</subject><subject>Animals</subject><subject>Avoidance Learning - drug effects</subject><subject>Avoidance Learning - physiology</subject><subject>Dopamine - analogs & derivatives</subject><subject>Dopamine - pharmacology</subject><subject>Dopamine - therapeutic use</subject><subject>Ethanol - administration & dosage</subject><subject>Habenula - drug effects</subject><subject>Habenula - metabolism</subject><subject>Male</subject><subject>Organ Culture Techniques</subject><subject>Rats</subject><subject>Rats, Long-Evans</subject><subject>Substance Withdrawal Syndrome - drug therapy</subject><subject>Substance Withdrawal Syndrome - etiology</subject><subject>Substance Withdrawal Syndrome - metabolism</subject><subject>TRPV Cation Channels - antagonists & inhibitors</subject><subject>TRPV Cation Channels - biosynthesis</subject><issn>0003-3022</issn><issn>1528-1175</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kc1u1DAUhS0EotPCGyDkJZuUxHacZIM0VC1FGn5UFbbWTXxDDB57ajsz4h360HiYUhUWeGPd6-8cX_sQ8qIqT6uya14vVx9PyweLyap-RBZVzdqiqpr6MVnkLi94ydgROY7xey6bmrdPyREvZSMFYwtye25xC8l4R_1IrwO4aNAleoUDbpIP9LNPuTZg6VdwxlpvNK3oxeyG3yLjaJqQriBhyMwl9OhmC_QDapN7kS63GKLZIn2LE2yND3GvWdrBT94WO5MmHWDn6BWk-Iw8GcFGfH63n5AvF-fXZ5fF6tO792fLVTGIltdFpyWTI-tk3XPdMWiFQNA9a7tBw6DliB1IzWXT9Jp3om96yVmGuBhbLkHwE_Lm4LuZ-zXqIT8wD682wawh_FQejPr7xJlJffNbJUXVdEJmg1d3BsHfzBiTWps4oLXg0M9RsYzVOZJ6j4oDOgQfY8Dx_pqqVPsgVQ5S_Rtklr18OOK96E9yGWgPwM7b_Pfxh513GNSEYNP0f-9f8ratEA</recordid><startdate>201904</startdate><enddate>201904</enddate><creator>Gregor, Danielle M</creator><creator>Zuo, Wanhong</creator><creator>Fu, Rao</creator><creator>Bekker, Alex</creator><creator>Ye, Jiang-Hong</creator><general>Copyright by , the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201904</creationdate><title>Elevation of Transient Receptor Potential Vanilloid 1 Function in the Lateral Habenula Mediates Aversive Behaviors in Alcohol-withdrawn Rats</title><author>Gregor, Danielle M ; Zuo, Wanhong ; Fu, Rao ; Bekker, Alex ; Ye, Jiang-Hong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4835-9d626f2965b3d92a844eadb289cdacd6fe9a6d3677bd394b7b63284434f836a43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Alcoholism - complications</topic><topic>Alcoholism - drug therapy</topic><topic>Alcoholism - metabolism</topic><topic>Animals</topic><topic>Avoidance Learning - drug effects</topic><topic>Avoidance Learning - physiology</topic><topic>Dopamine - analogs & derivatives</topic><topic>Dopamine - pharmacology</topic><topic>Dopamine - therapeutic use</topic><topic>Ethanol - administration & dosage</topic><topic>Habenula - drug effects</topic><topic>Habenula - metabolism</topic><topic>Male</topic><topic>Organ Culture Techniques</topic><topic>Rats</topic><topic>Rats, Long-Evans</topic><topic>Substance Withdrawal Syndrome - drug therapy</topic><topic>Substance Withdrawal Syndrome - etiology</topic><topic>Substance Withdrawal Syndrome - metabolism</topic><topic>TRPV Cation Channels - antagonists & inhibitors</topic><topic>TRPV Cation Channels - biosynthesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gregor, Danielle M</creatorcontrib><creatorcontrib>Zuo, Wanhong</creatorcontrib><creatorcontrib>Fu, Rao</creatorcontrib><creatorcontrib>Bekker, Alex</creatorcontrib><creatorcontrib>Ye, Jiang-Hong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Anesthesiology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gregor, Danielle M</au><au>Zuo, Wanhong</au><au>Fu, Rao</au><au>Bekker, Alex</au><au>Ye, Jiang-Hong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Elevation of Transient Receptor Potential Vanilloid 1 Function in the Lateral Habenula Mediates Aversive Behaviors in Alcohol-withdrawn Rats</atitle><jtitle>Anesthesiology (Philadelphia)</jtitle><addtitle>Anesthesiology</addtitle><date>2019-04</date><risdate>2019</risdate><volume>130</volume><issue>4</issue><spage>592</spage><epage>608</epage><pages>592-608</pages><issn>0003-3022</issn><eissn>1528-1175</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><notes>These authors contributed equally to the work.</notes><abstract>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 TRPV1 agonist capsaicin (3 μM) produced a weaker potentiation in Withdrawn than Naïve rats (spontaneous excitatory postsynaptic currentsby 203.6 ± 124.7% [n = 20] vs. 415.2 ± 424.3% [n = 15], P < 0.001; firing38.1 ± 14.7% [n = 11] vs. 73.9 ± 41.9% [n = 11], P < 0.001). Conversely, capsaicin’s actions in Naïve but not in Withdrawn rats were significantly attenuated by the pretreatment of TRPV1 endogenous agonist N-Oleoyldopamine. In Withdrawn rats, intra-habenula infusion of TRPV1 antagonists attenuated hyperalgesia and anxiety-like behaviors, decreased alcohol consumption upon resuming drinking, and elicited a conditioned place preference.
CONCLUSIONS:Enhanced TRPV1 function may contribute to increased glutamatergic transmission and activity of lateral habenula neurons, resulting in the aberrant behaviors during ethanol withdrawal.</abstract><cop>United States</cop><pub>Copyright by , the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc</pub><pmid>30676422</pmid><doi>10.1097/ALN.0000000000002615</doi><tpages>17</tpages><oa>free_for_read</oa></addata></record> |
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| 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 |
| title | Elevation of Transient Receptor Potential Vanilloid 1 Function in the Lateral Habenula Mediates Aversive Behaviors in Alcohol-withdrawn Rats |
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