Sex Differences in Regional Brain Glucose Metabolism Following Opioid Withdrawal and Replacement
Methadone and buprenorphine are currently the most common pharmacological treatments for opioid dependence. Interestingly, the clinical response to these drugs appears to be sex specific. That is, females exhibit superior therapeutic efficacy, defined as extended periods of abstinence and longer tim...
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| Veröffentlicht in: | Neuropsychopharmacology (New York, N.Y.) N.Y.), 2017-08, Vol.42 (9), p.1841-1849 |
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| creator | Santoro, Giovanni C Carrion, Joseph Patel, Krishna Vilchez, Crystal Veith, Jennifer Brodie, Jonathan D Dewey, Stephen L |
| description | Methadone and buprenorphine are currently the most common pharmacological treatments for opioid dependence. Interestingly, the clinical response to these drugs appears to be sex specific. That is, females exhibit superior therapeutic efficacy, defined as extended periods of abstinence and longer time to relapse, compared with males. However, the underlying metabolic effects of opioid withdrawal and replacement have not been examined. Therefore, using
FDG and microPET, we measured differences in regional brain glucose metabolism in males and females following morphine withdrawal and subsequent methadone or buprenorphine replacement. In both males and females, spontaneous opioid withdrawal altered glucose metabolism in regions associated with reward and drug dependence. Specifically, metabolic increases in the thalamus, as well as metabolic decreases in insular cortex and the periaqueductal gray, were noted. However, compared with males, females exhibited increased metabolism in the preoptic area, primary motor cortex, and the amygdala, and decreased metabolism in the caudate/putamen and medial geniculate nucleus. Methadone and buprenorphine initially abolished these changes uniformly, but subsequently produced their own regional metabolic alterations that varied by treatment and sex. Compared with sex-matched control animals undergoing spontaneous opioid withdrawal, male animals treated with methadone exhibited increased caudate/putamen metabolism, whereas buprenorphine produced increased ventral striatum and motor cortex metabolism in females, and increased ventral striatum and somatosensory cortex metabolism in males. Notably, when treatment effects were compared between sexes, methadone-treated females showed increased cingulate cortex metabolism, whereas buprenorphine-treated females showed decreased metabolism in cingulate cortex and increased metabolism in the globus pallidus. Perhaps the initial similarities in males and females underlie early therapeutic efficacy, whereas these posttreatment sex differences contribute to clinical treatment failure more commonly experienced by the former. |
| doi_str_mv | 10.1038/npp.2017.69 |
| format | Article |
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FDG and microPET, we measured differences in regional brain glucose metabolism in males and females following morphine withdrawal and subsequent methadone or buprenorphine replacement. In both males and females, spontaneous opioid withdrawal altered glucose metabolism in regions associated with reward and drug dependence. Specifically, metabolic increases in the thalamus, as well as metabolic decreases in insular cortex and the periaqueductal gray, were noted. However, compared with males, females exhibited increased metabolism in the preoptic area, primary motor cortex, and the amygdala, and decreased metabolism in the caudate/putamen and medial geniculate nucleus. Methadone and buprenorphine initially abolished these changes uniformly, but subsequently produced their own regional metabolic alterations that varied by treatment and sex. Compared with sex-matched control animals undergoing spontaneous opioid withdrawal, male animals treated with methadone exhibited increased caudate/putamen metabolism, whereas buprenorphine produced increased ventral striatum and motor cortex metabolism in females, and increased ventral striatum and somatosensory cortex metabolism in males. Notably, when treatment effects were compared between sexes, methadone-treated females showed increased cingulate cortex metabolism, whereas buprenorphine-treated females showed decreased metabolism in cingulate cortex and increased metabolism in the globus pallidus. Perhaps the initial similarities in males and females underlie early therapeutic efficacy, whereas these posttreatment sex differences contribute to clinical treatment failure more commonly experienced by the former.</description><identifier>ISSN: 0893-133X</identifier><identifier>EISSN: 1740-634X</identifier><identifier>DOI: 10.1038/npp.2017.69</identifier><identifier>PMID: 28393895</identifier><language>eng</language><publisher>England: Nature Publishing Group</publisher><subject>Amygdala ; Animals ; Brain ; Buprenorphine ; Cortex (cingulate) ; Cortex (insular) ; Cortex (motor) ; Drug dependence ; Drug therapy ; Drug withdrawal ; Females ; Gender differences ; Globus pallidus ; Glucose ; Glucose metabolism ; Heroin ; Males ; Medial geniculate body ; Metabolism ; Methadone ; Morphine ; Motor task performance ; Narcotics ; Neostriatum ; Opioids ; Original ; Periaqueductal gray area ; Preoptic area ; Putamen ; Reinforcement ; Sex ; Sex differences ; Sexual behavior ; Somatosensory cortex ; Thalamus</subject><ispartof>Neuropsychopharmacology (New York, N.Y.), 2017-08, Vol.42 (9), p.1841-1849</ispartof><rights>Copyright Nature Publishing Group Aug 2017</rights><rights>Copyright © 2017 American College of Neuropsychopharmacology 2017 American College of Neuropsychopharmacology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c409t-603c5e48fee90a34ca2ee9b3f4e9ab69a4aca3f8f6fcd78bc581379b6634eef23</citedby><cites>FETCH-LOGICAL-c409t-603c5e48fee90a34ca2ee9b3f4e9ab69a4aca3f8f6fcd78bc581379b6634eef23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520789/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520789/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28393895$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Santoro, Giovanni C</creatorcontrib><creatorcontrib>Carrion, Joseph</creatorcontrib><creatorcontrib>Patel, Krishna</creatorcontrib><creatorcontrib>Vilchez, Crystal</creatorcontrib><creatorcontrib>Veith, Jennifer</creatorcontrib><creatorcontrib>Brodie, Jonathan D</creatorcontrib><creatorcontrib>Dewey, Stephen L</creatorcontrib><title>Sex Differences in Regional Brain Glucose Metabolism Following Opioid Withdrawal and Replacement</title><title>Neuropsychopharmacology (New York, N.Y.)</title><addtitle>Neuropsychopharmacology</addtitle><description>Methadone and buprenorphine are currently the most common pharmacological treatments for opioid dependence. Interestingly, the clinical response to these drugs appears to be sex specific. That is, females exhibit superior therapeutic efficacy, defined as extended periods of abstinence and longer time to relapse, compared with males. However, the underlying metabolic effects of opioid withdrawal and replacement have not been examined. Therefore, using
FDG and microPET, we measured differences in regional brain glucose metabolism in males and females following morphine withdrawal and subsequent methadone or buprenorphine replacement. In both males and females, spontaneous opioid withdrawal altered glucose metabolism in regions associated with reward and drug dependence. Specifically, metabolic increases in the thalamus, as well as metabolic decreases in insular cortex and the periaqueductal gray, were noted. However, compared with males, females exhibited increased metabolism in the preoptic area, primary motor cortex, and the amygdala, and decreased metabolism in the caudate/putamen and medial geniculate nucleus. Methadone and buprenorphine initially abolished these changes uniformly, but subsequently produced their own regional metabolic alterations that varied by treatment and sex. Compared with sex-matched control animals undergoing spontaneous opioid withdrawal, male animals treated with methadone exhibited increased caudate/putamen metabolism, whereas buprenorphine produced increased ventral striatum and motor cortex metabolism in females, and increased ventral striatum and somatosensory cortex metabolism in males. Notably, when treatment effects were compared between sexes, methadone-treated females showed increased cingulate cortex metabolism, whereas buprenorphine-treated females showed decreased metabolism in cingulate cortex and increased metabolism in the globus pallidus. Perhaps the initial similarities in males and females underlie early therapeutic efficacy, whereas these posttreatment sex differences contribute to clinical treatment failure more commonly experienced by the former.</description><subject>Amygdala</subject><subject>Animals</subject><subject>Brain</subject><subject>Buprenorphine</subject><subject>Cortex (cingulate)</subject><subject>Cortex (insular)</subject><subject>Cortex (motor)</subject><subject>Drug dependence</subject><subject>Drug therapy</subject><subject>Drug withdrawal</subject><subject>Females</subject><subject>Gender differences</subject><subject>Globus pallidus</subject><subject>Glucose</subject><subject>Glucose metabolism</subject><subject>Heroin</subject><subject>Males</subject><subject>Medial geniculate body</subject><subject>Metabolism</subject><subject>Methadone</subject><subject>Morphine</subject><subject>Motor task performance</subject><subject>Narcotics</subject><subject>Neostriatum</subject><subject>Opioids</subject><subject>Original</subject><subject>Periaqueductal gray area</subject><subject>Preoptic area</subject><subject>Putamen</subject><subject>Reinforcement</subject><subject>Sex</subject><subject>Sex differences</subject><subject>Sexual behavior</subject><subject>Somatosensory cortex</subject><subject>Thalamus</subject><issn>0893-133X</issn><issn>1740-634X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpdkc1vFSEUxYnR2NenK_dmEjdNzDxhYBjYmNhqq0lNEz9id8gwl1caBkaYae1_X15aG3UF5P445957EHpB8IZgKt6Eado0mHQbLh-hFekYrjll54_RCgtJa0Lp-R7az_kSY9J2XDxFe42gkgrZrtDPr_C7eu-shQTBQK5cqL7A1sWgfXWYdHme-MXEDNVnmHUfvctjdRy9j9cubKuzyUU3VD_cfDEkfV0-6TAUhclrAyOE-Rl6YrXP8Pz-XKPvxx--HX2sT89OPh29O60Nw3KuOaamBSYsgMSaMqObcuupZSB1z6Vm2mhqheXWDJ3oTSsI7WTPy6gAtqFr9PZOd1r6EQZTrJP2akpu1OlGRe3Uv5XgLtQ2Xqm2bXBXFrVGB_cCKf5aIM9qdNmA9zpAXLIiQhSvpsW8oK_-Qy_jksrGCiWJoEyykswavb6jTIo5J7APzRCsdsmpkpzaJaf4zv7l3_0_sH-iorcd_pbd</recordid><startdate>20170801</startdate><enddate>20170801</enddate><creator>Santoro, Giovanni C</creator><creator>Carrion, Joseph</creator><creator>Patel, Krishna</creator><creator>Vilchez, Crystal</creator><creator>Veith, Jennifer</creator><creator>Brodie, Jonathan D</creator><creator>Dewey, Stephen L</creator><general>Nature Publishing Group</general><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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170801</creationdate><title>Sex Differences in Regional Brain Glucose Metabolism Following Opioid Withdrawal and Replacement</title><author>Santoro, Giovanni C ; 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FDG and microPET, we measured differences in regional brain glucose metabolism in males and females following morphine withdrawal and subsequent methadone or buprenorphine replacement. In both males and females, spontaneous opioid withdrawal altered glucose metabolism in regions associated with reward and drug dependence. Specifically, metabolic increases in the thalamus, as well as metabolic decreases in insular cortex and the periaqueductal gray, were noted. However, compared with males, females exhibited increased metabolism in the preoptic area, primary motor cortex, and the amygdala, and decreased metabolism in the caudate/putamen and medial geniculate nucleus. Methadone and buprenorphine initially abolished these changes uniformly, but subsequently produced their own regional metabolic alterations that varied by treatment and sex. Compared with sex-matched control animals undergoing spontaneous opioid withdrawal, male animals treated with methadone exhibited increased caudate/putamen metabolism, whereas buprenorphine produced increased ventral striatum and motor cortex metabolism in females, and increased ventral striatum and somatosensory cortex metabolism in males. Notably, when treatment effects were compared between sexes, methadone-treated females showed increased cingulate cortex metabolism, whereas buprenorphine-treated females showed decreased metabolism in cingulate cortex and increased metabolism in the globus pallidus. Perhaps the initial similarities in males and females underlie early therapeutic efficacy, whereas these posttreatment sex differences contribute to clinical treatment failure more commonly experienced by the former.</abstract><cop>England</cop><pub>Nature Publishing Group</pub><pmid>28393895</pmid><doi>10.1038/npp.2017.69</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amygdala Animals Brain Buprenorphine Cortex (cingulate) Cortex (insular) Cortex (motor) Drug dependence Drug therapy Drug withdrawal Females Gender differences Globus pallidus Glucose Glucose metabolism Heroin Males Medial geniculate body Metabolism Methadone Morphine Motor task performance Narcotics Neostriatum Opioids Original Periaqueductal gray area Preoptic area Putamen Reinforcement Sex Sex differences Sexual behavior Somatosensory cortex Thalamus |
| title | Sex Differences in Regional Brain Glucose Metabolism Following Opioid Withdrawal and Replacement |
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