The Expression of Contextual Fear Conditioning Involves Activation of an NMDA Receptor–Nitric Oxide Pathway in the Medial Prefrontal Cortex
The ventral portion of medial prefrontal cortex (vMPFC) is involved in contextual fear-conditioning expression in rats. In the present study, we investigated the role of local N-methyl-D-aspartic acid (NMDA) glutamate receptors and nitric oxide (NO) in vMPFC on the behavioral (freezing) and cardiova...
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| Veröffentlicht in: | Cerebral cortex (New York, N.Y. 1991) N.Y. 1991), 2008-09, Vol.18 (9), p.2027-2035 |
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| container_title | Cerebral cortex (New York, N.Y. 1991) |
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| creator | Moraes Resstel, Leonardo Barbosa de Aguiar Corrêa, Fernando Morgan Guimarães, Francisco Silveira |
| description | The ventral portion of medial prefrontal cortex (vMPFC) is involved in contextual fear-conditioning expression in rats. In the present study, we investigated the role of local N-methyl-D-aspartic acid (NMDA) glutamate receptors and nitric oxide (NO) in vMPFC on the behavioral (freezing) and cardiovascular (increase of arterial pressure and heart rate) responses of rats exposed to a context fear conditioning. The results showed that both freezing and cardiovascular responses to contextual fear conditioning were reduced by bilateral administration of NMDA receptor antagonist LY235959 (4 nmol/200 nL) into the vMPFC before reexposition to conditioned chamber. Bilateral inhibition of neuronal NO synthase (nNOS) by local vMPFC administration of the Nω-propyl-L-arginine (N-propyl, 0.04 nmol/200 nL) or the NO scavenger carboxy-PTIO (1 nmol/200 nL) caused similar results, inhibiting the fear responses. We also investigated the effects of inhibiting glutamate- and NO-mediated neurotransmission in the vMPFC at the time of aversive context exposure on reexposure to the same context. It was observed that the 1st exposure results in a significant attenuation of the fear responses on reexposure in vehicle-treated animals, which was not modified by the drugs. The present results suggest that a vMPFC NMDA–NO pathway may play an important role on expression of contextual fear conditioning. |
| doi_str_mv | 10.1093/cercor/bhm232 |
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In the present study, we investigated the role of local N-methyl-D-aspartic acid (NMDA) glutamate receptors and nitric oxide (NO) in vMPFC on the behavioral (freezing) and cardiovascular (increase of arterial pressure and heart rate) responses of rats exposed to a context fear conditioning. The results showed that both freezing and cardiovascular responses to contextual fear conditioning were reduced by bilateral administration of NMDA receptor antagonist LY235959 (4 nmol/200 nL) into the vMPFC before reexposition to conditioned chamber. Bilateral inhibition of neuronal NO synthase (nNOS) by local vMPFC administration of the Nω-propyl-L-arginine (N-propyl, 0.04 nmol/200 nL) or the NO scavenger carboxy-PTIO (1 nmol/200 nL) caused similar results, inhibiting the fear responses. We also investigated the effects of inhibiting glutamate- and NO-mediated neurotransmission in the vMPFC at the time of aversive context exposure on reexposure to the same context. It was observed that the 1st exposure results in a significant attenuation of the fear responses on reexposure in vehicle-treated animals, which was not modified by the drugs. The present results suggest that a vMPFC NMDA–NO pathway may play an important role on expression of contextual fear conditioning.</description><identifier>ISSN: 1047-3211</identifier><identifier>EISSN: 1460-2199</identifier><identifier>DOI: 10.1093/cercor/bhm232</identifier><identifier>PMID: 18158326</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Animals ; Arginine - analogs & derivatives ; Arginine - pharmacology ; Benzoates - pharmacology ; Blood Pressure - drug effects ; Blood Pressure - physiology ; cardiovascular system ; Conditioning (Psychology) - drug effects ; Conditioning (Psychology) - physiology ; Excitatory Amino Acid Antagonists - pharmacology ; Fear - physiology ; fear conditioning ; freezing ; Freezing Reaction, Cataleptic - physiology ; glutamatergic system ; Glutamic Acid - metabolism ; Heart Rate - drug effects ; Heart Rate - physiology ; Imidazoles - pharmacology ; infralimbic cortex ; Isoquinolines - pharmacology ; Male ; nitric oxide ; Nitric Oxide - metabolism ; Prefrontal Cortex - physiology ; Quinoxalines - pharmacology ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors ; Receptors, N-Methyl-D-Aspartate - metabolism ; Synaptic Transmission - drug effects ; Synaptic Transmission - physiology</subject><ispartof>Cerebral cortex (New York, N.Y. 1991), 2008-09, Vol.18 (9), p.2027-2035</ispartof><rights>2007 The Authors 2008</rights><rights>2007 The Authors</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c514t-1e15fb8b7723024fa6e6bd1d0ff9a705554c8b039da159875aafc800269434bd3</citedby><cites>FETCH-LOGICAL-c514t-1e15fb8b7723024fa6e6bd1d0ff9a705554c8b039da159875aafc800269434bd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18158326$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Moraes Resstel, Leonardo Barbosa</creatorcontrib><creatorcontrib>de Aguiar Corrêa, Fernando Morgan</creatorcontrib><creatorcontrib>Guimarães, Francisco Silveira</creatorcontrib><title>The Expression of Contextual Fear Conditioning Involves Activation of an NMDA Receptor–Nitric Oxide Pathway in the Medial Prefrontal Cortex</title><title>Cerebral cortex (New York, N.Y. 1991)</title><addtitle>Cereb Cortex</addtitle><description>The ventral portion of medial prefrontal cortex (vMPFC) is involved in contextual fear-conditioning expression in rats. In the present study, we investigated the role of local N-methyl-D-aspartic acid (NMDA) glutamate receptors and nitric oxide (NO) in vMPFC on the behavioral (freezing) and cardiovascular (increase of arterial pressure and heart rate) responses of rats exposed to a context fear conditioning. The results showed that both freezing and cardiovascular responses to contextual fear conditioning were reduced by bilateral administration of NMDA receptor antagonist LY235959 (4 nmol/200 nL) into the vMPFC before reexposition to conditioned chamber. Bilateral inhibition of neuronal NO synthase (nNOS) by local vMPFC administration of the Nω-propyl-L-arginine (N-propyl, 0.04 nmol/200 nL) or the NO scavenger carboxy-PTIO (1 nmol/200 nL) caused similar results, inhibiting the fear responses. We also investigated the effects of inhibiting glutamate- and NO-mediated neurotransmission in the vMPFC at the time of aversive context exposure on reexposure to the same context. It was observed that the 1st exposure results in a significant attenuation of the fear responses on reexposure in vehicle-treated animals, which was not modified by the drugs. The present results suggest that a vMPFC NMDA–NO pathway may play an important role on expression of contextual fear conditioning.</description><subject>Animals</subject><subject>Arginine - analogs & derivatives</subject><subject>Arginine - pharmacology</subject><subject>Benzoates - pharmacology</subject><subject>Blood Pressure - drug effects</subject><subject>Blood Pressure - physiology</subject><subject>cardiovascular system</subject><subject>Conditioning (Psychology) - drug effects</subject><subject>Conditioning (Psychology) - physiology</subject><subject>Excitatory Amino Acid Antagonists - pharmacology</subject><subject>Fear - physiology</subject><subject>fear conditioning</subject><subject>freezing</subject><subject>Freezing Reaction, Cataleptic - physiology</subject><subject>glutamatergic system</subject><subject>Glutamic Acid - metabolism</subject><subject>Heart Rate - drug effects</subject><subject>Heart Rate - physiology</subject><subject>Imidazoles - pharmacology</subject><subject>infralimbic cortex</subject><subject>Isoquinolines - pharmacology</subject><subject>Male</subject><subject>nitric oxide</subject><subject>Nitric Oxide - metabolism</subject><subject>Prefrontal Cortex - physiology</subject><subject>Quinoxalines - pharmacology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</subject><subject>Receptors, N-Methyl-D-Aspartate - metabolism</subject><subject>Synaptic Transmission - drug effects</subject><subject>Synaptic Transmission - physiology</subject><issn>1047-3211</issn><issn>1460-2199</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkstu1DAUhiMEohdYskUWi4pNqI8d57JBGk1bplI7rVARFRvLcZyOS8YOtjOd7ngBVrwhT4JHGZXLpisf63z-f59LkrwC_A5wRQ-lctK6w3qxJJQ8SXYhy3FKoKqexhhnRUoJwE6y5_0txlAQRp4nO1ACKynJd5MfVwuFjte9U95ra5Bt0dSaoNZhEB06UcJt7o0OManNDTo1K9utlEcTGfRKhO0bYdD8_GiCPiqp-mDdr-8_5zo4LdHFWjcKXYqwuBP3SBsUouG5anSUv3SqddEthlProumL5FkrOq9ebs_95NPJ8dV0lp5dfDidTs5SySALKShgbV3WRUEoJlkrcpXXDTS4bStRYMZYJssa06oRwKqyYEK0ssSY5FVGs7qh-8n7Ubcf6qVqpDLBiY73Ti-Fu-dWaP5vxugFv7ErThgUgMsocLAVcPbboHzgS-2l6jphlB083xhhVlaPggQwxYDzCL75D7y1gzOxCxxiCTlk5cY2HSHprPexew9fBsw368DHdeDjOkT-9d91_qG384_A2xGwQ_-o1tZb-zipB1i4rzwvaMH47PoLh8_l9ewoy_ic_gZFgdKG</recordid><startdate>20080901</startdate><enddate>20080901</enddate><creator>Moraes Resstel, Leonardo Barbosa</creator><creator>de Aguiar Corrêa, Fernando Morgan</creator><creator>Guimarães, Francisco Silveira</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>BSCLL</scope><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>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20080901</creationdate><title>The Expression of Contextual Fear Conditioning Involves Activation of an NMDA Receptor–Nitric Oxide Pathway in the Medial Prefrontal Cortex</title><author>Moraes Resstel, Leonardo Barbosa ; de Aguiar Corrêa, Fernando Morgan ; Guimarães, Francisco Silveira</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c514t-1e15fb8b7723024fa6e6bd1d0ff9a705554c8b039da159875aafc800269434bd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Arginine - analogs & derivatives</topic><topic>Arginine - pharmacology</topic><topic>Benzoates - pharmacology</topic><topic>Blood Pressure - drug effects</topic><topic>Blood Pressure - physiology</topic><topic>cardiovascular system</topic><topic>Conditioning (Psychology) - drug effects</topic><topic>Conditioning (Psychology) - physiology</topic><topic>Excitatory Amino Acid Antagonists - pharmacology</topic><topic>Fear - physiology</topic><topic>fear conditioning</topic><topic>freezing</topic><topic>Freezing Reaction, Cataleptic - physiology</topic><topic>glutamatergic system</topic><topic>Glutamic Acid - metabolism</topic><topic>Heart Rate - drug effects</topic><topic>Heart Rate - physiology</topic><topic>Imidazoles - pharmacology</topic><topic>infralimbic cortex</topic><topic>Isoquinolines - pharmacology</topic><topic>Male</topic><topic>nitric oxide</topic><topic>Nitric Oxide - metabolism</topic><topic>Prefrontal Cortex - physiology</topic><topic>Quinoxalines - pharmacology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</topic><topic>Receptors, N-Methyl-D-Aspartate - metabolism</topic><topic>Synaptic Transmission - drug effects</topic><topic>Synaptic Transmission - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Moraes Resstel, Leonardo Barbosa</creatorcontrib><creatorcontrib>de Aguiar Corrêa, Fernando Morgan</creatorcontrib><creatorcontrib>Guimarães, Francisco Silveira</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cerebral cortex (New York, N.Y. 1991)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moraes Resstel, Leonardo Barbosa</au><au>de Aguiar Corrêa, Fernando Morgan</au><au>Guimarães, Francisco Silveira</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Expression of Contextual Fear Conditioning Involves Activation of an NMDA Receptor–Nitric Oxide Pathway in the Medial Prefrontal Cortex</atitle><jtitle>Cerebral cortex (New York, N.Y. 1991)</jtitle><addtitle>Cereb Cortex</addtitle><date>2008-09-01</date><risdate>2008</risdate><volume>18</volume><issue>9</issue><spage>2027</spage><epage>2035</epage><pages>2027-2035</pages><issn>1047-3211</issn><eissn>1460-2199</eissn><abstract>The ventral portion of medial prefrontal cortex (vMPFC) is involved in contextual fear-conditioning expression in rats. In the present study, we investigated the role of local N-methyl-D-aspartic acid (NMDA) glutamate receptors and nitric oxide (NO) in vMPFC on the behavioral (freezing) and cardiovascular (increase of arterial pressure and heart rate) responses of rats exposed to a context fear conditioning. The results showed that both freezing and cardiovascular responses to contextual fear conditioning were reduced by bilateral administration of NMDA receptor antagonist LY235959 (4 nmol/200 nL) into the vMPFC before reexposition to conditioned chamber. Bilateral inhibition of neuronal NO synthase (nNOS) by local vMPFC administration of the Nω-propyl-L-arginine (N-propyl, 0.04 nmol/200 nL) or the NO scavenger carboxy-PTIO (1 nmol/200 nL) caused similar results, inhibiting the fear responses. We also investigated the effects of inhibiting glutamate- and NO-mediated neurotransmission in the vMPFC at the time of aversive context exposure on reexposure to the same context. It was observed that the 1st exposure results in a significant attenuation of the fear responses on reexposure in vehicle-treated animals, which was not modified by the drugs. The present results suggest that a vMPFC NMDA–NO pathway may play an important role on expression of contextual fear conditioning.</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>18158326</pmid><doi>10.1093/cercor/bhm232</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Animals Arginine - analogs & derivatives Arginine - pharmacology Benzoates - pharmacology Blood Pressure - drug effects Blood Pressure - physiology cardiovascular system Conditioning (Psychology) - drug effects Conditioning (Psychology) - physiology Excitatory Amino Acid Antagonists - pharmacology Fear - physiology fear conditioning freezing Freezing Reaction, Cataleptic - physiology glutamatergic system Glutamic Acid - metabolism Heart Rate - drug effects Heart Rate - physiology Imidazoles - pharmacology infralimbic cortex Isoquinolines - pharmacology Male nitric oxide Nitric Oxide - metabolism Prefrontal Cortex - physiology Quinoxalines - pharmacology Rats Rats, Wistar Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors Receptors, N-Methyl-D-Aspartate - metabolism Synaptic Transmission - drug effects Synaptic Transmission - physiology |
| title | The Expression of Contextual Fear Conditioning Involves Activation of an NMDA Receptor–Nitric Oxide Pathway in the Medial Prefrontal Cortex |
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