{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:13:31Z","timestamp":1792188811341,"version":"4.4.0"},"reference-count":79,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,11,8]],"date-time":"2012-11-08T00:00:00Z","timestamp":1352332800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"explicit-label\"><jats:list-item><jats:p>Clinical diagnosis of Huntington's disease (HD) is determined on the basis of motor symptoms; however, the pre\u2010motor stages of the disease are commonly associated with psychiatric alterations including depression and anxiety.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Using the R6\/1 transgenic mouse model of HD, this study is the first report on the effects of environmental enrichment (EE) at a very early stage on a broad range of behavioural tests assessing stress\u2010related measures.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Environmental enrichment did not prevent despair\u2010 and anhedonia\u2010like behaviours displayed by HD mice. However, EE reduced anxiety levels and corrected altered stress responses observed in HD mice.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Despite the enhanced hypothermic response to the serotonin 5\u2010HT<jats:sub>1A<\/jats:sub>receptor agonist 8\u2010OH\u2010DPAT exhibited by HD mice, we found a reduction in 5\u2010HT<jats:sub>1A<\/jats:sub>receptor mediated stimulation of [<jats:sup>35<\/jats:sup>S]GTP\u2010\u03b3\u2010S binding in the dorsal raphe nucleus and the hippocampus of HD animals.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Our data suggest that early EE has beneficial effects on the anxiety\u2010like, but not on the depression\u2010like, behaviours in HD mice. We also provide evidence that 8\u2010OH\u2010DPAT induced hypothermia could be mediated by other targets besides the serotonin 5\u2010HT<jats:sub>1A<\/jats:sub>receptors.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><jats:p><jats:bold>Abstract\u2002<\/jats:bold>Psychiatric disorders such as depression and anxiety are reported in patients with Huntington's disease (HD). Recent studies suggest beneficial effects of environmental enrichment (EE) on HD progression possibly through the serotonergic system. We investigated the potential effectiveness of EE in correcting the affective\u2010like phenotype of female R6\/1 HD mice. In addition to a behavioural battery of tests assessing depression and anxiety\u2010related endophenotypes, we recorded physiological measures, including body temperature regulation and defecation rate as indices of stress reactivity. Finally, following identification of changes in serotonin (5\u2010HT) receptor gene expression we measured the function of 5\u2010HT<jats:sub>1A<\/jats:sub>auto\u2010 and hetero\u2010receptors. We found that 8\u2010week\u2010old female HD mice exhibited higher immobility time in the forced swimming test and a decreased preference for saccharin solution. EE did not correct those depressive\u2010like behaviours but reduced anxiety\u2010related measures in unconditioned approach\/avoidance conflict situations. Defecation rate in a large open field and change in temperature during exposure to the tail suspension test were both enhanced in HD compared to wild\u2010type animals. Despite the enhanced hypothermic response to the 5\u2010HT<jats:sub>1A<\/jats:sub>receptor agonist 8\u2010OH\u2010DPAT exhibited by HD mice, we found a reduction in 5\u2010HT<jats:sub>1A<\/jats:sub>receptor\u2010mediated stimulation of [<jats:sup>35<\/jats:sup>S]GTP\u2010\u03b3\u2010S binding in the dorsal raphe nucleus and the hippocampus of HD animals. EE did not change 5\u2010HT<jats:sub>1A<\/jats:sub>receptor function. Our data suggest that early EE has beneficial effects on the anxiety\u2010like, but not on depression\u2010like, behaviours in HD. This is the first evidence that these affective endophenotypes can be dissociated via this form of environmental stimulation. As 5\u2010HT<jats:sub>1A<\/jats:sub>receptor dysfunction was not affected by EE, this receptor is unlikely to underlie the anxiety\u2010related phenotype of HD. However, the specific regulatory role of the 5\u2010HT<jats:sub>1A<\/jats:sub>autoreceptor in mediating depressive\u2010like behaviour in HD remains to be elucidated. Interestingly, by comparing<jats:italic>in vivo<\/jats:italic>and<jats:italic>in vitro<\/jats:italic>results, our findings suggest that 8\u2010OH\u2010DPAT\u2010induced hypothermia could be mediated by other targets besides the 5\u2010HT<jats:sub>1A<\/jats:sub>autoreceptor, including hippocampal 5\u2010HT<jats:sub>7<\/jats:sub>receptors.<\/jats:p>","DOI":"10.1113\/jphysiol.2012.239798","type":"journal-article","created":{"date-parts":[[2012,10,9]],"date-time":"2012-10-09T05:34:23Z","timestamp":1349760863000},"page":"41-55","source":"Crossref","is-referenced-by-count":44,"title":["Differential effects of early environmental enrichment on emotionality related behaviours in Huntington's disease transgenic mice"],"prefix":"10.1113","volume":"591","author":[{"given":"Thibault","family":"Renoir","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terence Y.C.","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Mo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Chevarin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Lanfumey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Hannan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,11,8]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2009.03.012"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2009.09.001"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-2543"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2005.09.020"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1991.tb12342.x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl094"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2011.04.006"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2011.107"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867054367220"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2008.06230.x"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2010.07.003"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004330"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2010.06.030"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2012.03.007"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2009.10.001"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2012.58"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2006.11.034"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4132-03.2004"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.31887\/DCNS.2008.10.3\/pgorwood"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2012.02.015"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0953-816x.2001.01767.x"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/026988110201600201"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-009-1626-0"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2004.01.031"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703855"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/YIC.0b013e3283348018"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2006.103309"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2012.02.027"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2008.07.031"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2008.04.006"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2008.05.001"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2004.03597.x"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2006.04715.x"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019498"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3956(03)00004-9"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012188"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2007.04.054"},{"key":"e_1_2_6_39_1","first-page":"7","article-title":"Depression's multiple comorbidities explained by (neuro)inflammatory and oxidative & nitrosative stress pathways","volume":"32","author":"Maes M","year":"2011","journal-title":"Neuroendocrinol Lett"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81369-0"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.64.1.116"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1971"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2270"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145711000940"},{"key":"e_1_2_6_45_1","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/S0022-3565(24)35339-X","article-title":"5\u2010Hydroxytryptamine(1A) receptor\u2010stimulated [(35)S]GTPgammaS binding in rat brain: absence of regional differences in coupling efficiency","volume":"292","author":"Meller E","year":"2000","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2004.01173.x"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2003.03070.x"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.2741\/3677"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2647"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2007.11.006"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1970"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.2174\/187152410791196341"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2011.11.063"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn385"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1176\/jnp.17.4.496"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2006.04985.x"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21736"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(97)00317-3"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2007.07.001"},{"key":"e_1_2_6_60_1","article-title":"Effects of environmental manipulations in genetically targeted animal models of affective disorders","author":"Renoir T","year":"2012","journal-title":"Neurobiol Dis"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2011.10.003"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01567.x"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022133"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01489.x"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2010.07.013"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1097\/PSY.0b013e318244fb82"},{"key":"e_1_2_6_67_1","article-title":"Epigenetics of the depressed brain: role of histone acetylation and methylation","author":"Sun H","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"e_1_2_6_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90585-E"},{"key":"e_1_2_6_69_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.neuropsych.11030057"},{"key":"e_1_2_6_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23108"},{"key":"e_1_2_6_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/35008142"},{"key":"e_1_2_6_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.05.006"},{"key":"e_1_2_6_73_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v69n1116"},{"key":"e_1_2_6_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2010.08.006"},{"key":"e_1_2_6_75_1","article-title":"Involvement of BDNF in age\u2010dependent alterations in the hippocampus","volume":"2","author":"von Bohlen und Halbach O","year":"2010","journal-title":"Front Aging Neurosci"},{"key":"e_1_2_6_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2011.06.013"},{"key":"e_1_2_6_77_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009077"},{"key":"e_1_2_6_78_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.20658"},{"key":"e_1_2_6_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2011.04.052"},{"key":"e_1_2_6_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2005.01.001"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fjphysiol.2012.239798","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/jphysiol.2012.239798","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T06:37:30Z","timestamp":1744267050000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/jphysiol.2012.239798"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,11,8]]},"references-count":79,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,1]]}},"alternative-id":["10.1113\/jphysiol.2012.239798"],"URL":"https:\/\/doi.org\/10.1113\/jphysiol.2012.239798","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,11,8]]}}}