Effect of age on methylphenidate-induced conditioned taste avoidance and related BDNF/TrkB signaling in the insular cortex of the rat
Rationale Drug use and abuse is thought to be a function of the balance between its rewarding and aversive effects, such that the rewarding effects increase the likelihood of use while the drug’s dissociable aversive effects limit it. Adolescents exhibit a shift in this balance toward reward, which...
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| Veröffentlicht in: | Psychopharmacology 2014-04, Vol.231 (8), p.1493-1501 |
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| creator | Wetzell, B. Bradley Muller, Mirabella M. Cobuzzi, Jennifer L. Hurwitz, Zachary E. DeCicco-Skinner, Kathleen Riley, Anthony L. |
| description | Rationale
Drug use and abuse is thought to be a function of the balance between its rewarding and aversive effects, such that the rewarding effects increase the likelihood of use while the drug’s dissociable aversive effects limit it. Adolescents exhibit a shift in this balance toward reward, which may ultimately lead to increased use. Importantly, recent work shows that adolescents are also protected from the aversive effects of many abusable drugs as measured by conditioned taste avoidance (CTA). However, such effects of methylphenidate (MPH, widely prescribed to adolescents with ADHD) have not been characterized.
Objectives
The effect of age on MPH-induced CTA was assessed. In addition, MPH-induced changes in brain-derived neurotrophic factor (BDNF) activity in the insular cortex (IC) and central nucleus of the amygdala (CeA), known to be important to CTA, were examined and related to CTAs in adolescents and adults.
Methods
CTAs induced by MPH (0, 10, 18, and 32 mg/kg) were assessed in adolescent (
n
= 34) and adult (
n
= 33) male Sprague Dawley rats. Following MPH CTA, IC and CeA tissue was probed for differences in BDNF and tropomyosin-related kinase receptor-B (TrkB) using Western blots.
Results
Blunted expression of MPH CTA was observed in the adolescents versus adults, which correlated with generally attenuated adolescent BDNF/TrkB activity in the IC, but the drug effects ran contrary to the expression of CTA.
Conclusions
Adolescents are protected from the aversive effects of MPH versus adults, but further work is needed to characterize the possible involvement of BDNF/TrkB. |
| doi_str_mv | 10.1007/s00213-014-3500-y |
| format | Article |
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Drug use and abuse is thought to be a function of the balance between its rewarding and aversive effects, such that the rewarding effects increase the likelihood of use while the drug’s dissociable aversive effects limit it. Adolescents exhibit a shift in this balance toward reward, which may ultimately lead to increased use. Importantly, recent work shows that adolescents are also protected from the aversive effects of many abusable drugs as measured by conditioned taste avoidance (CTA). However, such effects of methylphenidate (MPH, widely prescribed to adolescents with ADHD) have not been characterized.
Objectives
The effect of age on MPH-induced CTA was assessed. In addition, MPH-induced changes in brain-derived neurotrophic factor (BDNF) activity in the insular cortex (IC) and central nucleus of the amygdala (CeA), known to be important to CTA, were examined and related to CTAs in adolescents and adults.
Methods
CTAs induced by MPH (0, 10, 18, and 32 mg/kg) were assessed in adolescent (
n
= 34) and adult (
n
= 33) male Sprague Dawley rats. Following MPH CTA, IC and CeA tissue was probed for differences in BDNF and tropomyosin-related kinase receptor-B (TrkB) using Western blots.
Results
Blunted expression of MPH CTA was observed in the adolescents versus adults, which correlated with generally attenuated adolescent BDNF/TrkB activity in the IC, but the drug effects ran contrary to the expression of CTA.
Conclusions
Adolescents are protected from the aversive effects of MPH versus adults, but further work is needed to characterize the possible involvement of BDNF/TrkB.</description><identifier>ISSN: 0033-3158</identifier><identifier>EISSN: 1432-2072</identifier><identifier>DOI: 10.1007/s00213-014-3500-y</identifier><identifier>PMID: 24563186</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Age ; Animals ; Avoidance Learning - drug effects ; Avoidance Learning - physiology ; Biomedical and Life Sciences ; Biomedicine ; Blotting, Western ; Brain ; Brain-derived neurotrophic factor ; Brain-Derived Neurotrophic Factor - metabolism ; Central Amygdaloid Nucleus - drug effects ; Central Amygdaloid Nucleus - growth & development ; Central Amygdaloid Nucleus - physiology ; Cerebral cortex ; Cerebral Cortex - drug effects ; Cerebral Cortex - growth & development ; Cerebral Cortex - physiology ; Complications and side effects ; Conditioning, Classical - drug effects ; Conditioning, Classical - physiology ; Development and progression ; Dopamine Uptake Inhibitors - pharmacology ; Dosage and administration ; Dose-Response Relationship, Drug ; Eating - drug effects ; Eating - physiology ; Genetic aspects ; Male ; Methylphenidate ; Methylphenidate - pharmacology ; Methylphenidate hydrochloride ; Neurosciences ; Original Investigation ; Pharmacology/Toxicology ; Phosphorylation ; Physiological aspects ; Psychiatry ; Psychopharmacology ; Rats, Sprague-Dawley ; Receptor, trkB - metabolism ; Risk factors ; Rodents ; Saccharin - administration & dosage ; Signal Transduction ; Taste disorders ; Taste Perception - drug effects ; Taste Perception - physiology</subject><ispartof>Psychopharmacology, 2014-04, Vol.231 (8), p.1493-1501</ispartof><rights>Springer-Verlag Berlin Heidelberg 2014</rights><rights>COPYRIGHT 2014 Springer</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c472t-357235f7a53516fac5310e05ed2d6a0687081bdcc7ee2714e1271733e5caa8043</citedby><cites>FETCH-LOGICAL-c472t-357235f7a53516fac5310e05ed2d6a0687081bdcc7ee2714e1271733e5caa8043</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00213-014-3500-y$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00213-014-3500-y$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24563186$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wetzell, B. Bradley</creatorcontrib><creatorcontrib>Muller, Mirabella M.</creatorcontrib><creatorcontrib>Cobuzzi, Jennifer L.</creatorcontrib><creatorcontrib>Hurwitz, Zachary E.</creatorcontrib><creatorcontrib>DeCicco-Skinner, Kathleen</creatorcontrib><creatorcontrib>Riley, Anthony L.</creatorcontrib><title>Effect of age on methylphenidate-induced conditioned taste avoidance and related BDNF/TrkB signaling in the insular cortex of the rat</title><title>Psychopharmacology</title><addtitle>Psychopharmacology</addtitle><addtitle>Psychopharmacology (Berl)</addtitle><description>Rationale
Drug use and abuse is thought to be a function of the balance between its rewarding and aversive effects, such that the rewarding effects increase the likelihood of use while the drug’s dissociable aversive effects limit it. Adolescents exhibit a shift in this balance toward reward, which may ultimately lead to increased use. Importantly, recent work shows that adolescents are also protected from the aversive effects of many abusable drugs as measured by conditioned taste avoidance (CTA). However, such effects of methylphenidate (MPH, widely prescribed to adolescents with ADHD) have not been characterized.
Objectives
The effect of age on MPH-induced CTA was assessed. In addition, MPH-induced changes in brain-derived neurotrophic factor (BDNF) activity in the insular cortex (IC) and central nucleus of the amygdala (CeA), known to be important to CTA, were examined and related to CTAs in adolescents and adults.
Methods
CTAs induced by MPH (0, 10, 18, and 32 mg/kg) were assessed in adolescent (
n
= 34) and adult (
n
= 33) male Sprague Dawley rats. Following MPH CTA, IC and CeA tissue was probed for differences in BDNF and tropomyosin-related kinase receptor-B (TrkB) using Western blots.
Results
Blunted expression of MPH CTA was observed in the adolescents versus adults, which correlated with generally attenuated adolescent BDNF/TrkB activity in the IC, but the drug effects ran contrary to the expression of CTA.
Conclusions
Adolescents are protected from the aversive effects of MPH versus adults, but further work is needed to characterize the possible involvement of BDNF/TrkB.</description><subject>Age</subject><subject>Animals</subject><subject>Avoidance Learning - drug effects</subject><subject>Avoidance Learning - physiology</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Blotting, Western</subject><subject>Brain</subject><subject>Brain-derived neurotrophic factor</subject><subject>Brain-Derived Neurotrophic Factor - metabolism</subject><subject>Central Amygdaloid Nucleus - drug effects</subject><subject>Central Amygdaloid Nucleus - growth & development</subject><subject>Central Amygdaloid Nucleus - physiology</subject><subject>Cerebral cortex</subject><subject>Cerebral Cortex - drug effects</subject><subject>Cerebral Cortex - growth & development</subject><subject>Cerebral Cortex - physiology</subject><subject>Complications and side effects</subject><subject>Conditioning, Classical - drug effects</subject><subject>Conditioning, Classical - physiology</subject><subject>Development and progression</subject><subject>Dopamine Uptake Inhibitors - pharmacology</subject><subject>Dosage and administration</subject><subject>Dose-Response Relationship, Drug</subject><subject>Eating - drug effects</subject><subject>Eating - physiology</subject><subject>Genetic aspects</subject><subject>Male</subject><subject>Methylphenidate</subject><subject>Methylphenidate - pharmacology</subject><subject>Methylphenidate hydrochloride</subject><subject>Neurosciences</subject><subject>Original Investigation</subject><subject>Pharmacology/Toxicology</subject><subject>Phosphorylation</subject><subject>Physiological aspects</subject><subject>Psychiatry</subject><subject>Psychopharmacology</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptor, trkB - metabolism</subject><subject>Risk factors</subject><subject>Rodents</subject><subject>Saccharin - administration & dosage</subject><subject>Signal Transduction</subject><subject>Taste disorders</subject><subject>Taste Perception - drug effects</subject><subject>Taste Perception - physiology</subject><issn>0033-3158</issn><issn>1432-2072</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</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>eNp1kV1vFCEUhonR2HX1B3hjSLzxZlo-hmFu29qqSaM39ZpQODNLnYUVmMb9Af5vz7j1MwoJEHjeFw4vIc85O-aM6ZPCmOCyYbxtpGKs2T8gK95K0QimxUOyYkzKRnLVH5EnpdwybG3fPiZHolWd5H23Il8vhgFcpWmgdgSaIt1C3eyn3QZi8LZCE6KfHXjqUvShhhRxXW2pQO1dQiQ6XEVPM0yIe3r2-v3lyXX-dEZLGKOdQhxpiLRuAKcyTzajVa7wZblz2c22PiWPBjsVeHY_r8nHy4vr87fN1Yc3785PrxrXalGxSC2kGrRVUvFusE5JzoAp8MJ3lnW9Zj2_8c5pAKF5CxxHLSUoZ23PWrkmrw6-u5w-z1Cq2YbiYJpshDQXw9FWKyFRsyYv_0Jv05yxnu8Uk5p3nf5FjXYCE-KQarZuMTWnUguBD5QMqeN_UNg9bAP-KwwB9_8Q8IPA5VRKhsHsctjavDecmSV6c4jeYPRmid7sUfPi_sHzzRb8T8WPrBEQB6DgURwh_1bRf12_AWc2t2c</recordid><startdate>20140401</startdate><enddate>20140401</enddate><creator>Wetzell, B. Bradley</creator><creator>Muller, Mirabella M.</creator><creator>Cobuzzi, Jennifer L.</creator><creator>Hurwitz, Zachary E.</creator><creator>DeCicco-Skinner, Kathleen</creator><creator>Riley, Anthony L.</creator><general>Springer Berlin Heidelberg</general><general>Springer</general><general>Springer Nature B.V</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>3V.</scope><scope>7QG</scope><scope>7QR</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope></search><sort><creationdate>20140401</creationdate><title>Effect of age on methylphenidate-induced conditioned taste avoidance and related BDNF/TrkB signaling in the insular cortex of the rat</title><author>Wetzell, B. Bradley ; Muller, Mirabella M. ; Cobuzzi, Jennifer L. ; Hurwitz, Zachary E. ; DeCicco-Skinner, Kathleen ; Riley, Anthony L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c472t-357235f7a53516fac5310e05ed2d6a0687081bdcc7ee2714e1271733e5caa8043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Age</topic><topic>Animals</topic><topic>Avoidance Learning - drug effects</topic><topic>Avoidance Learning - physiology</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Blotting, Western</topic><topic>Brain</topic><topic>Brain-derived neurotrophic factor</topic><topic>Brain-Derived Neurotrophic Factor - metabolism</topic><topic>Central Amygdaloid Nucleus - drug effects</topic><topic>Central Amygdaloid Nucleus - growth & development</topic><topic>Central Amygdaloid Nucleus - physiology</topic><topic>Cerebral cortex</topic><topic>Cerebral Cortex - drug effects</topic><topic>Cerebral Cortex - growth & development</topic><topic>Cerebral Cortex - physiology</topic><topic>Complications and side effects</topic><topic>Conditioning, Classical - drug effects</topic><topic>Conditioning, Classical - physiology</topic><topic>Development and progression</topic><topic>Dopamine Uptake Inhibitors - pharmacology</topic><topic>Dosage and administration</topic><topic>Dose-Response Relationship, Drug</topic><topic>Eating - drug effects</topic><topic>Eating - physiology</topic><topic>Genetic aspects</topic><topic>Male</topic><topic>Methylphenidate</topic><topic>Methylphenidate - pharmacology</topic><topic>Methylphenidate hydrochloride</topic><topic>Neurosciences</topic><topic>Original Investigation</topic><topic>Pharmacology/Toxicology</topic><topic>Phosphorylation</topic><topic>Physiological aspects</topic><topic>Psychiatry</topic><topic>Psychopharmacology</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptor, trkB - metabolism</topic><topic>Risk factors</topic><topic>Rodents</topic><topic>Saccharin - administration & dosage</topic><topic>Signal Transduction</topic><topic>Taste disorders</topic><topic>Taste Perception - drug effects</topic><topic>Taste Perception - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wetzell, B. Bradley</creatorcontrib><creatorcontrib>Muller, Mirabella M.</creatorcontrib><creatorcontrib>Cobuzzi, Jennifer L.</creatorcontrib><creatorcontrib>Hurwitz, Zachary E.</creatorcontrib><creatorcontrib>DeCicco-Skinner, Kathleen</creatorcontrib><creatorcontrib>Riley, Anthony L.</creatorcontrib><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>Animal Behavior Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Nursing & Allied Health Database</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>Technology Research Database</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>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</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><jtitle>Psychopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wetzell, B. Bradley</au><au>Muller, Mirabella M.</au><au>Cobuzzi, Jennifer L.</au><au>Hurwitz, Zachary E.</au><au>DeCicco-Skinner, Kathleen</au><au>Riley, Anthony L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of age on methylphenidate-induced conditioned taste avoidance and related BDNF/TrkB signaling in the insular cortex of the rat</atitle><jtitle>Psychopharmacology</jtitle><stitle>Psychopharmacology</stitle><addtitle>Psychopharmacology (Berl)</addtitle><date>2014-04-01</date><risdate>2014</risdate><volume>231</volume><issue>8</issue><spage>1493</spage><epage>1501</epage><pages>1493-1501</pages><issn>0033-3158</issn><eissn>1432-2072</eissn><abstract>Rationale
Drug use and abuse is thought to be a function of the balance between its rewarding and aversive effects, such that the rewarding effects increase the likelihood of use while the drug’s dissociable aversive effects limit it. Adolescents exhibit a shift in this balance toward reward, which may ultimately lead to increased use. Importantly, recent work shows that adolescents are also protected from the aversive effects of many abusable drugs as measured by conditioned taste avoidance (CTA). However, such effects of methylphenidate (MPH, widely prescribed to adolescents with ADHD) have not been characterized.
Objectives
The effect of age on MPH-induced CTA was assessed. In addition, MPH-induced changes in brain-derived neurotrophic factor (BDNF) activity in the insular cortex (IC) and central nucleus of the amygdala (CeA), known to be important to CTA, were examined and related to CTAs in adolescents and adults.
Methods
CTAs induced by MPH (0, 10, 18, and 32 mg/kg) were assessed in adolescent (
n
= 34) and adult (
n
= 33) male Sprague Dawley rats. Following MPH CTA, IC and CeA tissue was probed for differences in BDNF and tropomyosin-related kinase receptor-B (TrkB) using Western blots.
Results
Blunted expression of MPH CTA was observed in the adolescents versus adults, which correlated with generally attenuated adolescent BDNF/TrkB activity in the IC, but the drug effects ran contrary to the expression of CTA.
Conclusions
Adolescents are protected from the aversive effects of MPH versus adults, but further work is needed to characterize the possible involvement of BDNF/TrkB.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>24563186</pmid><doi>10.1007/s00213-014-3500-y</doi><tpages>9</tpages></addata></record> |
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| ispartof | Psychopharmacology, 2014-04, Vol.231 (8), p.1493-1501 |
| issn | 0033-3158 1432-2072 |
| language | eng |
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| subjects | Age Animals Avoidance Learning - drug effects Avoidance Learning - physiology Biomedical and Life Sciences Biomedicine Blotting, Western Brain Brain-derived neurotrophic factor Brain-Derived Neurotrophic Factor - metabolism Central Amygdaloid Nucleus - drug effects Central Amygdaloid Nucleus - growth & development Central Amygdaloid Nucleus - physiology Cerebral cortex Cerebral Cortex - drug effects Cerebral Cortex - growth & development Cerebral Cortex - physiology Complications and side effects Conditioning, Classical - drug effects Conditioning, Classical - physiology Development and progression Dopamine Uptake Inhibitors - pharmacology Dosage and administration Dose-Response Relationship, Drug Eating - drug effects Eating - physiology Genetic aspects Male Methylphenidate Methylphenidate - pharmacology Methylphenidate hydrochloride Neurosciences Original Investigation Pharmacology/Toxicology Phosphorylation Physiological aspects Psychiatry Psychopharmacology Rats, Sprague-Dawley Receptor, trkB - metabolism Risk factors Rodents Saccharin - administration & dosage Signal Transduction Taste disorders Taste Perception - drug effects Taste Perception - physiology |
| title | Effect of age on methylphenidate-induced conditioned taste avoidance and related BDNF/TrkB signaling in the insular cortex of the rat |
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