Compulsive alcohol drinking in rodents is associated with altered representations of behavioral control and seeking in dorsal medial prefrontal cortex.
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ABSTRACT:
SUBMITTER: Timme NM
PROVIDER: S-EPMC9271071 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:RationaleBrain iron accumulation has been observed in neuropsychiatric disorders and shown to be related to neurodegeneration.ObjectivesIn this study, we used quantitative susceptibility mapping (QSM), an emerging MRI technique developed for quantifying tissue magnetic susceptibility, to examine brain iron accumulation in individuals with alcohol use disorder (AUD) and its relation to compulsive drinking.MethodsBased on our previous projects, QSM was performed as a secondary analysis with gradient echo sequence images, in 186 individuals with AUD and 274 healthy participants. Whole-brain susceptibility values were calculated with morphology-enabled dipole inversion and referenced to the cerebrospinal fluid. Then, the susceptibility maps were compared between AUD individuals and healthy participants. The relationship between drinking patterns and susceptibility was explored.ResultsWhole-brain analyses showed that the susceptibility in the dorsal striatum (putamen and caudate) among AUD individuals was higher than healthy participants and was positively related to the Obsessive Compulsive Drinking Scale (OCDS) scores and the amount of drinking in the past three months.ConclusionsIncreased susceptibility suggests higher iron accumulation in the dorsal striatum in AUD. This surrogate for the brain iron level was linearly associated with the compulsive drinking pattern and the recent amount of drinking, which provides us a new clinical perspective in relation to brain iron accumulation, and also might indicate an association of AUD with neuroinflammation as a consequence of brain iron accumulation. The iron accumulation in the striatum is further relevant for functional imaging studies in AUD by potentially producing signal dropout and artefacts in fMRI images.
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Project description:Obsessive-compulsive disorder (OCD) affects ∼1 to 3% of the world's population. However, the neural mechanisms underlying the excessive checking symptoms in OCD are not fully understood. Using viral neuronal tracing in mice, we found that glutamatergic neurons from the basolateral amygdala (BLAGlu) project onto both medial prefrontal cortex glutamate (mPFCGlu) and GABA (mPFCGABA) neurons that locally innervate mPFCGlu neurons. Next, we developed an OCD checking mouse model with quinpirole-induced repetitive checking behaviors. This model demonstrated decreased glutamatergic mPFC microcircuit activity regulated by enhanced BLAGlu inputs. Optical or chemogenetic manipulations of this maladaptive circuitry restored the behavioral response. These findings were verified in a mouse functional magnetic resonance imaging (fMRI) study, in which the BLA-mPFC functional connectivity was increased in OCD mice. Together, these findings define a unique BLAGlu→mPFCGABA→Glu circuit that controls the checking symptoms of OCD.
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