Trehalose induced antidepressant-like effects and autophagy enhancement in mice
Rationale The disaccharide trehalose protects cells from hypoxic and anoxic injury and suppresses protein aggregation. In vivo studies with trehalose show cellular and behavioral beneficial effects in animal models of neurodegenerative diseases. Moreover, trehalose was shown to enhance autophagy, a...
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| Veröffentlicht in: | Psychopharmacology 2013-09, Vol.229 (2), p.367-375 |
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| creator | Kara, N. Z. Toker, L. Agam, G. Anderson, G. W. Belmaker, R. H. Einat, H. |
| description | Rationale
The disaccharide trehalose protects cells from hypoxic and anoxic injury and suppresses protein aggregation. In vivo studies with trehalose show cellular and behavioral beneficial effects in animal models of neurodegenerative diseases. Moreover, trehalose was shown to enhance autophagy, a process that had been recently suggested to be involved in the therapeutic action of antidepressant and mood-stabilizing drugs.
Objective
The present study was therefore designed to explore antidepressant and mood-stabilizing activity of trehalose in animal models for depression and mania.
Methods
Trehalose 1 or 2 % was administered for 3 weeks as a drinking solution to Black Swiss mice (a model of manic-like behaviors) or 2 % to ICR mice and their behavior evaluated in a number of tests related to depression or mania. The effects of trehalose were compared with similar chronic administration of the disaccharide maltose as well as with a vehicle (water) control.
Results
Chronic administration of trehalose resulted in a reduction of frontal cortex p62/beclin-1 ratio suggesting enhancement of autophagy. Trehalose had no mood-stabilizing effects on manic-like behavior in Black Swiss mice but instead augmented amphetamine-induced hyperactivity, an effect similar to antidepressant drugs. In ICR mice, trehalose did not alter spontaneous activity or amphetamine-induced hyperactivity but in two separate experiments had a significant effect to reduce immobility in the forced swim test, a standard screening test for antidepressant-like effects.
Conclusions
The results suggest that trehalose may have antidepressant-like properties. It is hypothesized that these behavioral changes could be related to trehalose effects to enhance autophagy. |
| doi_str_mv | 10.1007/s00213-013-3119-4 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_1439218138</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A343464097</galeid><sourcerecordid>A343464097</sourcerecordid><originalsourceid>FETCH-LOGICAL-c472t-b938af2a16e9f1685b833efedf373d7449f426d1f48b046c8c73a150f35096673</originalsourceid><addsrcrecordid>eNp1kcFO3DAQhq0KVLbbPkAvKBIXLgHb402c4woBrYTEBc6W1xnvhibOYieHfXsm2oW2CGxZtjzfP57xz9hPwS8E5-Vl4lwKyDktEKLK1Rc2EwpkLnkpj9iMc5giC33CvqX0xGkorb6yEwmFUpWAGbt_iLixbZ8wa0I9OqwzG4amxm3ElOiYt80fzNB7dEOiGMXHod9u7HqXYdjY4LDDMJA66xqH39mxt23CH4d9zh5vrh-ufuV397e_r5Z3uVOlHPJVBdp6aUWBlReFXqw0AHqsPZRQl1ScV7KohVd6xVXhtCvBigX3sOBVUZQwZ-f7vNvYP4-YBtM1yWHb2oD9mAx9QyWFFqAJPXuHPvVjDFTdRCkhuazgL7W2LZom-H6I1k1JzRIIKxSvpmcvPqBo1kjd9wF9Q_f_CcRe4GKfUkRvtrHpbNwZwc1kotmbaMhEM5loFGlODwWPqw7rN8WrawTIPZAoFNYY_-no06wvABukIQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1434120293</pqid></control><display><type>article</type><title>Trehalose induced antidepressant-like effects and autophagy enhancement in mice</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Kara, N. Z. ; Toker, L. ; Agam, G. ; Anderson, G. W. ; Belmaker, R. H. ; Einat, H.</creator><creatorcontrib>Kara, N. Z. ; Toker, L. ; Agam, G. ; Anderson, G. W. ; Belmaker, R. H. ; Einat, H.</creatorcontrib><description>Rationale
The disaccharide trehalose protects cells from hypoxic and anoxic injury and suppresses protein aggregation. In vivo studies with trehalose show cellular and behavioral beneficial effects in animal models of neurodegenerative diseases. Moreover, trehalose was shown to enhance autophagy, a process that had been recently suggested to be involved in the therapeutic action of antidepressant and mood-stabilizing drugs.
Objective
The present study was therefore designed to explore antidepressant and mood-stabilizing activity of trehalose in animal models for depression and mania.
Methods
Trehalose 1 or 2 % was administered for 3 weeks as a drinking solution to Black Swiss mice (a model of manic-like behaviors) or 2 % to ICR mice and their behavior evaluated in a number of tests related to depression or mania. The effects of trehalose were compared with similar chronic administration of the disaccharide maltose as well as with a vehicle (water) control.
Results
Chronic administration of trehalose resulted in a reduction of frontal cortex p62/beclin-1 ratio suggesting enhancement of autophagy. Trehalose had no mood-stabilizing effects on manic-like behavior in Black Swiss mice but instead augmented amphetamine-induced hyperactivity, an effect similar to antidepressant drugs. In ICR mice, trehalose did not alter spontaneous activity or amphetamine-induced hyperactivity but in two separate experiments had a significant effect to reduce immobility in the forced swim test, a standard screening test for antidepressant-like effects.
Conclusions
The results suggest that trehalose may have antidepressant-like properties. It is hypothesized that these behavioral changes could be related to trehalose effects to enhance autophagy.</description><identifier>ISSN: 0033-3158</identifier><identifier>EISSN: 1432-2072</identifier><identifier>DOI: 10.1007/s00213-013-3119-4</identifier><identifier>PMID: 23644913</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Amphetamine - toxicity ; Analysis of Variance ; Animals ; Antidepressants ; Antidepressive Agents - pharmacology ; Autophagy ; Autophagy (Cytology) ; Autophagy - drug effects ; Biomedical and Life Sciences ; Biomedicine ; Bipolar disorder ; Brain - drug effects ; Brain - metabolism ; Central Nervous System Stimulants - toxicity ; Dosage and administration ; Dose-Response Relationship, Drug ; Drinking Behavior - drug effects ; Exploratory Behavior - drug effects ; Gene Expression Regulation - drug effects ; Health aspects ; Hyperkinesis - chemically induced ; Hyperkinesis - drug therapy ; Intracellular Signaling Peptides and Proteins - metabolism ; Male ; Maltose - administration & dosage ; Mental depression ; Mice ; Mice, Inbred ICR ; Neurosciences ; Original Investigation ; Pharmacology/Toxicology ; Psychiatry ; Psychopharmacology ; Rodents ; Sweetening Agents - administration & dosage ; Swimming - psychology ; Transcription Factors - metabolism ; Trehalose ; Trehalose - pharmacology</subject><ispartof>Psychopharmacology, 2013-09, Vol.229 (2), p.367-375</ispartof><rights>Springer-Verlag Berlin Heidelberg 2013</rights><rights>COPYRIGHT 2013 Springer</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c472t-b938af2a16e9f1685b833efedf373d7449f426d1f48b046c8c73a150f35096673</citedby><cites>FETCH-LOGICAL-c472t-b938af2a16e9f1685b833efedf373d7449f426d1f48b046c8c73a150f35096673</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/s00213-013-3119-4$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00213-013-3119-4$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23644913$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kara, N. Z.</creatorcontrib><creatorcontrib>Toker, L.</creatorcontrib><creatorcontrib>Agam, G.</creatorcontrib><creatorcontrib>Anderson, G. W.</creatorcontrib><creatorcontrib>Belmaker, R. H.</creatorcontrib><creatorcontrib>Einat, H.</creatorcontrib><title>Trehalose induced antidepressant-like effects and autophagy enhancement in mice</title><title>Psychopharmacology</title><addtitle>Psychopharmacology</addtitle><addtitle>Psychopharmacology (Berl)</addtitle><description>Rationale
The disaccharide trehalose protects cells from hypoxic and anoxic injury and suppresses protein aggregation. In vivo studies with trehalose show cellular and behavioral beneficial effects in animal models of neurodegenerative diseases. Moreover, trehalose was shown to enhance autophagy, a process that had been recently suggested to be involved in the therapeutic action of antidepressant and mood-stabilizing drugs.
Objective
The present study was therefore designed to explore antidepressant and mood-stabilizing activity of trehalose in animal models for depression and mania.
Methods
Trehalose 1 or 2 % was administered for 3 weeks as a drinking solution to Black Swiss mice (a model of manic-like behaviors) or 2 % to ICR mice and their behavior evaluated in a number of tests related to depression or mania. The effects of trehalose were compared with similar chronic administration of the disaccharide maltose as well as with a vehicle (water) control.
Results
Chronic administration of trehalose resulted in a reduction of frontal cortex p62/beclin-1 ratio suggesting enhancement of autophagy. Trehalose had no mood-stabilizing effects on manic-like behavior in Black Swiss mice but instead augmented amphetamine-induced hyperactivity, an effect similar to antidepressant drugs. In ICR mice, trehalose did not alter spontaneous activity or amphetamine-induced hyperactivity but in two separate experiments had a significant effect to reduce immobility in the forced swim test, a standard screening test for antidepressant-like effects.
Conclusions
The results suggest that trehalose may have antidepressant-like properties. It is hypothesized that these behavioral changes could be related to trehalose effects to enhance autophagy.</description><subject>Amphetamine - toxicity</subject><subject>Analysis of Variance</subject><subject>Animals</subject><subject>Antidepressants</subject><subject>Antidepressive Agents - pharmacology</subject><subject>Autophagy</subject><subject>Autophagy (Cytology)</subject><subject>Autophagy - drug effects</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Bipolar disorder</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Central Nervous System Stimulants - toxicity</subject><subject>Dosage and administration</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drinking Behavior - drug effects</subject><subject>Exploratory Behavior - drug effects</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Health aspects</subject><subject>Hyperkinesis - chemically induced</subject><subject>Hyperkinesis - drug therapy</subject><subject>Intracellular Signaling Peptides and Proteins - metabolism</subject><subject>Male</subject><subject>Maltose - administration & dosage</subject><subject>Mental depression</subject><subject>Mice</subject><subject>Mice, Inbred ICR</subject><subject>Neurosciences</subject><subject>Original Investigation</subject><subject>Pharmacology/Toxicology</subject><subject>Psychiatry</subject><subject>Psychopharmacology</subject><subject>Rodents</subject><subject>Sweetening Agents - administration & dosage</subject><subject>Swimming - psychology</subject><subject>Transcription Factors - metabolism</subject><subject>Trehalose</subject><subject>Trehalose - pharmacology</subject><issn>0033-3158</issn><issn>1432-2072</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</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>eNp1kcFO3DAQhq0KVLbbPkAvKBIXLgHb402c4woBrYTEBc6W1xnvhibOYieHfXsm2oW2CGxZtjzfP57xz9hPwS8E5-Vl4lwKyDktEKLK1Rc2EwpkLnkpj9iMc5giC33CvqX0xGkorb6yEwmFUpWAGbt_iLixbZ8wa0I9OqwzG4amxm3ElOiYt80fzNB7dEOiGMXHod9u7HqXYdjY4LDDMJA66xqH39mxt23CH4d9zh5vrh-ufuV397e_r5Z3uVOlHPJVBdp6aUWBlReFXqw0AHqsPZRQl1ScV7KohVd6xVXhtCvBigX3sOBVUZQwZ-f7vNvYP4-YBtM1yWHb2oD9mAx9QyWFFqAJPXuHPvVjDFTdRCkhuazgL7W2LZom-H6I1k1JzRIIKxSvpmcvPqBo1kjd9wF9Q_f_CcRe4GKfUkRvtrHpbNwZwc1kotmbaMhEM5loFGlODwWPqw7rN8WrawTIPZAoFNYY_-no06wvABukIQ</recordid><startdate>20130901</startdate><enddate>20130901</enddate><creator>Kara, N. Z.</creator><creator>Toker, L.</creator><creator>Agam, G.</creator><creator>Anderson, G. W.</creator><creator>Belmaker, R. H.</creator><creator>Einat, H.</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>20130901</creationdate><title>Trehalose induced antidepressant-like effects and autophagy enhancement in mice</title><author>Kara, N. Z. ; Toker, L. ; Agam, G. ; Anderson, G. W. ; Belmaker, R. H. ; Einat, H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c472t-b938af2a16e9f1685b833efedf373d7449f426d1f48b046c8c73a150f35096673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Amphetamine - toxicity</topic><topic>Analysis of Variance</topic><topic>Animals</topic><topic>Antidepressants</topic><topic>Antidepressive Agents - pharmacology</topic><topic>Autophagy</topic><topic>Autophagy (Cytology)</topic><topic>Autophagy - drug effects</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Bipolar disorder</topic><topic>Brain - drug effects</topic><topic>Brain - metabolism</topic><topic>Central Nervous System Stimulants - toxicity</topic><topic>Dosage and administration</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drinking Behavior - drug effects</topic><topic>Exploratory Behavior - drug effects</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Health aspects</topic><topic>Hyperkinesis - chemically induced</topic><topic>Hyperkinesis - drug therapy</topic><topic>Intracellular Signaling Peptides and Proteins - metabolism</topic><topic>Male</topic><topic>Maltose - administration & dosage</topic><topic>Mental depression</topic><topic>Mice</topic><topic>Mice, Inbred ICR</topic><topic>Neurosciences</topic><topic>Original Investigation</topic><topic>Pharmacology/Toxicology</topic><topic>Psychiatry</topic><topic>Psychopharmacology</topic><topic>Rodents</topic><topic>Sweetening Agents - administration & dosage</topic><topic>Swimming - psychology</topic><topic>Transcription Factors - metabolism</topic><topic>Trehalose</topic><topic>Trehalose - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kara, N. Z.</creatorcontrib><creatorcontrib>Toker, L.</creatorcontrib><creatorcontrib>Agam, G.</creatorcontrib><creatorcontrib>Anderson, G. W.</creatorcontrib><creatorcontrib>Belmaker, R. H.</creatorcontrib><creatorcontrib>Einat, H.</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>ProQuest Nursing and Allied Health Journals</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health and Medical</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>ProQuest Psychology Journals</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>Kara, N. Z.</au><au>Toker, L.</au><au>Agam, G.</au><au>Anderson, G. W.</au><au>Belmaker, R. H.</au><au>Einat, H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Trehalose induced antidepressant-like effects and autophagy enhancement in mice</atitle><jtitle>Psychopharmacology</jtitle><stitle>Psychopharmacology</stitle><addtitle>Psychopharmacology (Berl)</addtitle><date>2013-09-01</date><risdate>2013</risdate><volume>229</volume><issue>2</issue><spage>367</spage><epage>375</epage><pages>367-375</pages><issn>0033-3158</issn><eissn>1432-2072</eissn><abstract>Rationale
The disaccharide trehalose protects cells from hypoxic and anoxic injury and suppresses protein aggregation. In vivo studies with trehalose show cellular and behavioral beneficial effects in animal models of neurodegenerative diseases. Moreover, trehalose was shown to enhance autophagy, a process that had been recently suggested to be involved in the therapeutic action of antidepressant and mood-stabilizing drugs.
Objective
The present study was therefore designed to explore antidepressant and mood-stabilizing activity of trehalose in animal models for depression and mania.
Methods
Trehalose 1 or 2 % was administered for 3 weeks as a drinking solution to Black Swiss mice (a model of manic-like behaviors) or 2 % to ICR mice and their behavior evaluated in a number of tests related to depression or mania. The effects of trehalose were compared with similar chronic administration of the disaccharide maltose as well as with a vehicle (water) control.
Results
Chronic administration of trehalose resulted in a reduction of frontal cortex p62/beclin-1 ratio suggesting enhancement of autophagy. Trehalose had no mood-stabilizing effects on manic-like behavior in Black Swiss mice but instead augmented amphetamine-induced hyperactivity, an effect similar to antidepressant drugs. In ICR mice, trehalose did not alter spontaneous activity or amphetamine-induced hyperactivity but in two separate experiments had a significant effect to reduce immobility in the forced swim test, a standard screening test for antidepressant-like effects.
Conclusions
The results suggest that trehalose may have antidepressant-like properties. It is hypothesized that these behavioral changes could be related to trehalose effects to enhance autophagy.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>23644913</pmid><doi>10.1007/s00213-013-3119-4</doi><tpages>9</tpages></addata></record> |
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| ispartof | Psychopharmacology, 2013-09, Vol.229 (2), p.367-375 |
| issn | 0033-3158 1432-2072 |
| language | eng |
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| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Amphetamine - toxicity Analysis of Variance Animals Antidepressants Antidepressive Agents - pharmacology Autophagy Autophagy (Cytology) Autophagy - drug effects Biomedical and Life Sciences Biomedicine Bipolar disorder Brain - drug effects Brain - metabolism Central Nervous System Stimulants - toxicity Dosage and administration Dose-Response Relationship, Drug Drinking Behavior - drug effects Exploratory Behavior - drug effects Gene Expression Regulation - drug effects Health aspects Hyperkinesis - chemically induced Hyperkinesis - drug therapy Intracellular Signaling Peptides and Proteins - metabolism Male Maltose - administration & dosage Mental depression Mice Mice, Inbred ICR Neurosciences Original Investigation Pharmacology/Toxicology Psychiatry Psychopharmacology Rodents Sweetening Agents - administration & dosage Swimming - psychology Transcription Factors - metabolism Trehalose Trehalose - pharmacology |
| title | Trehalose induced antidepressant-like effects and autophagy enhancement in mice |
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