A mu-opioid receptor single nucleotide polymorphism in rhesus monkey: association with stress response and aggression
Variations in the human mu-opioid receptor gene have driven exploration of their biochemical, physiological and pathological relevance. We investigated the existence of variations in the nonhuman primate mu-opioid receptor gene to determine whether nonhuman primates can model genotype/phenotype asso...
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| Veröffentlicht in: | Molecular psychiatry 2004-01, Vol.9 (1), p.99-108 |
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| creator | Miller, G M Bendor, J Tiefenbacher, S Yang, H Novak, M A Madras, B K |
| description | Variations in the human mu-opioid receptor gene have driven exploration of their biochemical, physiological and pathological relevance. We investigated the existence of variations in the nonhuman primate mu-opioid receptor gene to determine whether nonhuman primates can model genotype/phenotype associations of relevance to humans. Similar to the A118G single nucleotide polymorphism (SNP) in the human mu-opioid receptor gene, a SNP discovered in the rhesus monkey mu-opioid receptor gene (C77G) alters an amino acid in the N-terminal arm of the receptor (arginine for proline at position 26). Two mu-opioid receptor coding regions isolated from a single heterozygous (C77/G77) rhesus monkey brain were expressed in HEK-293 cells and characterized in radioreceptor assays. Paralleling the findings of increased affinity of
β
-endorphin by the A118G allele in the human, the rhesus monkey mu-opioid receptor protein derived from the G77-containing clone demonstrated a 3.5-fold greater affinity for
β
-endorphin than the receptor derived from the C77-containing clone. An assay developed to assess the incidence of the C77G SNP in a behaviorally and physiologically characterized cohort of rhesus monkeys (
n
=32) indicated that 44% were homozygous for C77-containing alleles, 50% were heterozygous and 6% were homozygous for G77-containing alleles. The presence of G77-containing alleles was associated with significantly lower basal and ACTH-stimulated plasma cortisol levels (
P |
| doi_str_mv | 10.1038/sj.mp.4001378 |
| format | Article |
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β
-endorphin by the A118G allele in the human, the rhesus monkey mu-opioid receptor protein derived from the G77-containing clone demonstrated a 3.5-fold greater affinity for
β
-endorphin than the receptor derived from the C77-containing clone. An assay developed to assess the incidence of the C77G SNP in a behaviorally and physiologically characterized cohort of rhesus monkeys (
n
=32) indicated that 44% were homozygous for C77-containing alleles, 50% were heterozygous and 6% were homozygous for G77-containing alleles. The presence of G77-containing alleles was associated with significantly lower basal and ACTH-stimulated plasma cortisol levels (
P
<0.03–0.05 and
P
<0.02, respectively) and a significantly higher aggressive threat score (
P
<0.05)
in vivo
. In a cohort of 20 monkeys, a trend towards an inverse correlation between aggressive threat and plasma cortisol levels was observed. The findings suggest that mu-opioid receptor haplotypes in monkeys can contribute to individual variability in stress response and related aggression. The data support the use of nonhuman primates to investigate mu-opioid receptor genotype/phenotype relations of relevance to humans.</description><identifier>ISSN: 1359-4184</identifier><identifier>EISSN: 1476-5578</identifier><identifier>DOI: 10.1038/sj.mp.4001378</identifier><identifier>PMID: 14699447</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Aggression ; Aggressiveness ; Amino Acid Sequence ; Animals ; Behavioral psychophysiology ; Behavioral Sciences ; Biological and medical sciences ; Biological Psychology ; Cloning ; Endorphins ; Fundamental and applied biological sciences. Psychology ; Hormones ; Hormones and behavior ; Hydrocortisone - blood ; Macaca mulatta - genetics ; Medicine ; Medicine & Public Health ; Molecular Sequence Data ; Monkeys & apes ; Narcotics ; Neurosciences ; original-research-article ; Personality. Affectivity ; Pharmacotherapy ; Polymorphism ; Polymorphism, Single Nucleotide ; Protein Structure, Tertiary ; Proteins ; Psychiatry ; Psychology. Psychoanalysis. Psychiatry ; Psychology. Psychophysiology ; Receptors, Opioid, mu - chemistry ; Receptors, Opioid, mu - genetics ; Stress ; Stress, Physiological - genetics</subject><ispartof>Molecular psychiatry, 2004-01, Vol.9 (1), p.99-108</ispartof><rights>Springer Nature Limited 2004</rights><rights>2004 INIST-CNRS</rights><rights>COPYRIGHT 2004 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c477t-6c76a96aab2bd4d61cac11e3c3835feca14933ddbeeab5bb58e717dac07473383</citedby><cites>FETCH-LOGICAL-c477t-6c76a96aab2bd4d61cac11e3c3835feca14933ddbeeab5bb58e717dac07473383</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,4024,27923,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15421993$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14699447$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Miller, G M</creatorcontrib><creatorcontrib>Bendor, J</creatorcontrib><creatorcontrib>Tiefenbacher, S</creatorcontrib><creatorcontrib>Yang, H</creatorcontrib><creatorcontrib>Novak, M A</creatorcontrib><creatorcontrib>Madras, B K</creatorcontrib><title>A mu-opioid receptor single nucleotide polymorphism in rhesus monkey: association with stress response and aggression</title><title>Molecular psychiatry</title><addtitle>Mol Psychiatry</addtitle><addtitle>Mol Psychiatry</addtitle><description>Variations in the human mu-opioid receptor gene have driven exploration of their biochemical, physiological and pathological relevance. We investigated the existence of variations in the nonhuman primate mu-opioid receptor gene to determine whether nonhuman primates can model genotype/phenotype associations of relevance to humans. Similar to the A118G single nucleotide polymorphism (SNP) in the human mu-opioid receptor gene, a SNP discovered in the rhesus monkey mu-opioid receptor gene (C77G) alters an amino acid in the N-terminal arm of the receptor (arginine for proline at position 26). Two mu-opioid receptor coding regions isolated from a single heterozygous (C77/G77) rhesus monkey brain were expressed in HEK-293 cells and characterized in radioreceptor assays. Paralleling the findings of increased affinity of
β
-endorphin by the A118G allele in the human, the rhesus monkey mu-opioid receptor protein derived from the G77-containing clone demonstrated a 3.5-fold greater affinity for
β
-endorphin than the receptor derived from the C77-containing clone. An assay developed to assess the incidence of the C77G SNP in a behaviorally and physiologically characterized cohort of rhesus monkeys (
n
=32) indicated that 44% were homozygous for C77-containing alleles, 50% were heterozygous and 6% were homozygous for G77-containing alleles. The presence of G77-containing alleles was associated with significantly lower basal and ACTH-stimulated plasma cortisol levels (
P
<0.03–0.05 and
P
<0.02, respectively) and a significantly higher aggressive threat score (
P
<0.05)
in vivo
. In a cohort of 20 monkeys, a trend towards an inverse correlation between aggressive threat and plasma cortisol levels was observed. The findings suggest that mu-opioid receptor haplotypes in monkeys can contribute to individual variability in stress response and related aggression. The data support the use of nonhuman primates to investigate mu-opioid receptor genotype/phenotype relations of relevance to humans.</description><subject>Aggression</subject><subject>Aggressiveness</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Behavioral psychophysiology</subject><subject>Behavioral Sciences</subject><subject>Biological and medical sciences</subject><subject>Biological Psychology</subject><subject>Cloning</subject><subject>Endorphins</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hormones</subject><subject>Hormones and behavior</subject><subject>Hydrocortisone - blood</subject><subject>Macaca mulatta - genetics</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Molecular Sequence Data</subject><subject>Monkeys & apes</subject><subject>Narcotics</subject><subject>Neurosciences</subject><subject>original-research-article</subject><subject>Personality. Affectivity</subject><subject>Pharmacotherapy</subject><subject>Polymorphism</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Protein Structure, Tertiary</subject><subject>Proteins</subject><subject>Psychiatry</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychology. Psychophysiology</subject><subject>Receptors, Opioid, mu - chemistry</subject><subject>Receptors, Opioid, mu - genetics</subject><subject>Stress</subject><subject>Stress, Physiological - genetics</subject><issn>1359-4184</issn><issn>1476-5578</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkduL1DAUxoso7kUffVSCsL51bJqkSfdtWLzBgi_6XE7T05mMbVJzWmT-e7NM3QFBfEo43-871yx7xYsNL4R5T4fNOG1kUXChzZPskktd5Upp8zT9hapzyY28yK6IDolJonqeXXBZ1bWU-jJbtmxc8jC54DoW0eI0h8jI-d2AzC92wDC7DtkUhuMY4rR3NDLnWdwjLcTG4H_g8ZYBUbAOZhc8--XmPaM5IlHKSFPwhAx8x2C3ewgm5kX2rIeB8OX6XmffP374dvc5v__66cvd9j63Uus5r6yuoK4A2rLtZFdxC5ZzFFYYoXq0wGUtRNe1iNCqtlUGNdcd2EJLLRJ0nb075Z1i-Lkgzc3oyOIwgMewUGOKQmtVqv-C3BRCiJIn8O1f4CEs0achmrLkpRRSFwnanKAdDNg434c5QuodOhydDR57l-JbbowypZJlMuQng42BKGLfTNGNEI8NL5qHMzd0aMapWc-c-DdrF0s7Ynem17sm4GYFgCwMfQRvHZ25VJTXaXePnVKS_A7jeZx_VX59MniYl4iPGf_ovwESLMv_</recordid><startdate>200401</startdate><enddate>200401</enddate><creator>Miller, G M</creator><creator>Bendor, J</creator><creator>Tiefenbacher, S</creator><creator>Yang, H</creator><creator>Novak, M A</creator><creator>Madras, B K</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>IQODW</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>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7QG</scope><scope>7X8</scope></search><sort><creationdate>200401</creationdate><title>A mu-opioid receptor single nucleotide polymorphism in rhesus monkey: association with stress response and aggression</title><author>Miller, G M ; Bendor, J ; Tiefenbacher, S ; Yang, H ; Novak, M A ; Madras, B K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c477t-6c76a96aab2bd4d61cac11e3c3835feca14933ddbeeab5bb58e717dac07473383</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Aggression</topic><topic>Aggressiveness</topic><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Behavioral psychophysiology</topic><topic>Behavioral Sciences</topic><topic>Biological and medical sciences</topic><topic>Biological Psychology</topic><topic>Cloning</topic><topic>Endorphins</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hormones</topic><topic>Hormones and behavior</topic><topic>Hydrocortisone - blood</topic><topic>Macaca mulatta - genetics</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Molecular Sequence Data</topic><topic>Monkeys & apes</topic><topic>Narcotics</topic><topic>Neurosciences</topic><topic>original-research-article</topic><topic>Personality. Affectivity</topic><topic>Pharmacotherapy</topic><topic>Polymorphism</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Protein Structure, Tertiary</topic><topic>Proteins</topic><topic>Psychiatry</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychology. Psychophysiology</topic><topic>Receptors, Opioid, mu - chemistry</topic><topic>Receptors, Opioid, mu - genetics</topic><topic>Stress</topic><topic>Stress, Physiological - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Miller, G M</creatorcontrib><creatorcontrib>Bendor, J</creatorcontrib><creatorcontrib>Tiefenbacher, S</creatorcontrib><creatorcontrib>Yang, H</creatorcontrib><creatorcontrib>Novak, M A</creatorcontrib><creatorcontrib>Madras, B K</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>Animal Behavior Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular psychiatry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Miller, G M</au><au>Bendor, J</au><au>Tiefenbacher, S</au><au>Yang, H</au><au>Novak, M A</au><au>Madras, B K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A mu-opioid receptor single nucleotide polymorphism in rhesus monkey: association with stress response and aggression</atitle><jtitle>Molecular psychiatry</jtitle><stitle>Mol Psychiatry</stitle><addtitle>Mol Psychiatry</addtitle><date>2004-01</date><risdate>2004</risdate><volume>9</volume><issue>1</issue><spage>99</spage><epage>108</epage><pages>99-108</pages><issn>1359-4184</issn><eissn>1476-5578</eissn><abstract>Variations in the human mu-opioid receptor gene have driven exploration of their biochemical, physiological and pathological relevance. We investigated the existence of variations in the nonhuman primate mu-opioid receptor gene to determine whether nonhuman primates can model genotype/phenotype associations of relevance to humans. Similar to the A118G single nucleotide polymorphism (SNP) in the human mu-opioid receptor gene, a SNP discovered in the rhesus monkey mu-opioid receptor gene (C77G) alters an amino acid in the N-terminal arm of the receptor (arginine for proline at position 26). Two mu-opioid receptor coding regions isolated from a single heterozygous (C77/G77) rhesus monkey brain were expressed in HEK-293 cells and characterized in radioreceptor assays. Paralleling the findings of increased affinity of
β
-endorphin by the A118G allele in the human, the rhesus monkey mu-opioid receptor protein derived from the G77-containing clone demonstrated a 3.5-fold greater affinity for
β
-endorphin than the receptor derived from the C77-containing clone. An assay developed to assess the incidence of the C77G SNP in a behaviorally and physiologically characterized cohort of rhesus monkeys (
n
=32) indicated that 44% were homozygous for C77-containing alleles, 50% were heterozygous and 6% were homozygous for G77-containing alleles. The presence of G77-containing alleles was associated with significantly lower basal and ACTH-stimulated plasma cortisol levels (
P
<0.03–0.05 and
P
<0.02, respectively) and a significantly higher aggressive threat score (
P
<0.05)
in vivo
. In a cohort of 20 monkeys, a trend towards an inverse correlation between aggressive threat and plasma cortisol levels was observed. The findings suggest that mu-opioid receptor haplotypes in monkeys can contribute to individual variability in stress response and related aggression. The data support the use of nonhuman primates to investigate mu-opioid receptor genotype/phenotype relations of relevance to humans.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>14699447</pmid><doi>10.1038/sj.mp.4001378</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| issn | 1359-4184 1476-5578 |
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| subjects | Aggression Aggressiveness Amino Acid Sequence Animals Behavioral psychophysiology Behavioral Sciences Biological and medical sciences Biological Psychology Cloning Endorphins Fundamental and applied biological sciences. Psychology Hormones Hormones and behavior Hydrocortisone - blood Macaca mulatta - genetics Medicine Medicine & Public Health Molecular Sequence Data Monkeys & apes Narcotics Neurosciences original-research-article Personality. Affectivity Pharmacotherapy Polymorphism Polymorphism, Single Nucleotide Protein Structure, Tertiary Proteins Psychiatry Psychology. Psychoanalysis. Psychiatry Psychology. Psychophysiology Receptors, Opioid, mu - chemistry Receptors, Opioid, mu - genetics Stress Stress, Physiological - genetics |
| title | A mu-opioid receptor single nucleotide polymorphism in rhesus monkey: association with stress response and aggression |
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