Abstract:
BACKGROUND:GPR88 is an orphan G protein coupled receptor highly enriched in the striatum, and previous studies have focused on GPR88 function in striatal physiology. The receptor is also expressed in other brain areas, and here we examined whether GPR88 function extends beyond striatal-mediated responses. METHODS:We created Gpr88 knockout mice and examined both striatal and extrastriatal regions at molecular and cellular levels. We also tested striatum-, hippocampus-, and amygdala-dependent behaviors in Gpr88(-/-) mice using extensive behavioral testing. RESULTS:We found increased G protein coupling for delta opioid receptor (DOR) and mu opioid, but not other Gi/o coupled receptors, in the striatum of Gpr88 knockout mice. We also found modifications in gene transcription, dopamine and serotonin contents, and dendritic morphology inside and outside the striatum. Behavioral testing confirmed striatal deficits (hyperactivity, stereotypies, motor impairment in rotarod). In addition, mutant mice performed better in spatial tasks dependent on hippocampus (Y-maze, novel object recognition, dual solution cross-maze) and also showed markedly reduced levels of anxiety (elevated plus maze, marble burying, novelty suppressed feeding). Strikingly, chronic blockade of DOR using naltrindole partially improved motor coordination and normalized spatial navigation and anxiety of Gpr88(-/-) mice. CONCLUSIONS:We demonstrate that GPR88 is implicated in a large repertoire of behavioral responses that engage motor activity, spatial learning, and emotional processing. Our data also reveal functional antagonism between GPR88 and DOR activities in vivo. The therapeutic potential of GPR88 therefore extends to cognitive and anxiety disorders, possibly in interaction with other receptor systems.
journal_name
Biol Psychiatryjournal_title
Biological psychiatryauthors
Meirsman AC,Le Merrer J,Pellissier LP,Diaz J,Clesse D,Kieffer BL,Becker JAdoi
10.1016/j.biopsych.2015.05.020subject
Has Abstractpub_date
2016-06-01 00:00:00pages
917-27issue
11eissn
0006-3223issn
1873-2402pii
S0006-3223(15)00469-2journal_volume
79pub_type
杂志文章abstract:BACKGROUND:The anterior cingulate and medial prefrontal cortex play an important role in the inhibition of responses, as measured by the Stroop task, as well as in emotional regulation. Dysfunction of the anterior cingulate/medial prefrontal cortex has been implicated in posttraumatic stress disorder (PTSD). The purpos...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2003.10.001
更新日期:2004-03-15 00:00:00
abstract::Using auditory evoked responses, this work compares the reactivities to unimodal and crossmodal stimuli and the main neurocognitive functions most often disturbed in autism. With the aim of testing the hypothesis that the deficit in the ability to form crossmodal associations in autism is linked to a cognitive abnorma...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(92)90338-z
更新日期:1992-06-15 00:00:00
abstract::Somatostatin is a tetradecapeptide that is assuming increasing importance as a regulator of central nervous system activity. Originally identified as the hypothalamic growth hormone release-inhibiting factor, somatostatin has subsequently been shown to be extensively and selectively distributed throughout the central ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(86)90163-0
更新日期:1986-04-01 00:00:00
abstract:BACKGROUND:Subjects at increased risk for psychosis experience continuous variation in the intensity of subtle psychotic experiences in response to minor stressors. It was investigated whether this psychotic reactivity in individuals at risk for psychosis is the exophenotypic expression of an underlying endophenotype c...
journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章
doi:10.1016/j.biopsych.2005.02.012
更新日期:2005-07-15 00:00:00
abstract::Posttraumatic stress disorder (PTSD) is a stress-related psychiatric disorder that is thought to emerge from complex interactions among traumatic events and multiple genetic factors. Epigenetic regulation lies at the heart of these interactions and mediates the lasting effects of the environment on gene regulation. An...
journal_title:Biological psychiatry
pub_type: 杂志文章,评审
doi:10.1016/j.biopsych.2015.04.003
更新日期:2015-09-01 00:00:00
abstract:BACKGROUND:There is a paucity of neuroimaging data in pediatric-onset obsessive-compulsive disorder (OCD). This multimodal neuroimaging study aimed to identify structural gray (GM) and white matter (WM) microstructure changes in pediatric OCD. METHODS:We obtained structural and diffusion tensor magnetic resonance imag...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2011.06.032
更新日期:2011-12-01 00:00:00
abstract::The interaction between various neuroleptics and antiparkinsonian drugs was analyzed by measuring the neuroleptic plasma level before and after withdrawal of antiparkinsonian drugs. The population completing the study consisted of 32 chronic schizophrenics treated with chlorpromazine (8), levomepromazine (14), thiorid...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:
更新日期:1977-06-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2010.03.017
更新日期:2010-07-15 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2008.05.012
更新日期:2008-09-15 00:00:00
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pub_type: 杂志文章
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更新日期:2015-07-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2016.08.037
更新日期:2017-07-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2010.01.024
更新日期:2010-06-01 00:00:00
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journal_title:Biological psychiatry
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journal_title:Biological psychiatry
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更新日期:1998-10-15 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2010.07.033
更新日期:2010-12-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.biopsych.2006.01.019
更新日期:2006-07-15 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(03)00348-2
更新日期:2003-12-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.biopsych.2005.11.017
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journal_title:Biological psychiatry
pub_type: 杂志文章
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journal_title:Biological psychiatry
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doi:10.1016/j.biopsych.2006.07.039
更新日期:2007-07-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(87)90052-7
更新日期:1987-09-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
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更新日期:1990-05-15 00:00:00
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pub_type: 杂志文章
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更新日期:2013-01-15 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(99)00032-3
更新日期:1999-10-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:
更新日期:1983-02-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(87)90152-1
更新日期:1987-03-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
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更新日期:1990-06-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2006-05-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:
更新日期:1982-01-01 00:00:00