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Article
Open AccessLowering Hippocampal miR-29a Expression Slows Cognitive Decline and Reduces Beta-Amyloid Deposition in 5×FAD Mice
microRNA-29a (miR-29a) increases with age in humans and mice, and, in the brain, it has a role in neuronal maturation and response to inflammation. We previously found higher miR-29a levels in the human brain ...
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Article
Unique pharmacodynamic properties and low abuse liability of the µ-opioid receptor ligand (S)-methadone
(R,S)-methadone ((R,S)-MTD) is a µ-opioid receptor (MOR) agonist comprised of (R)-MTD and (S)-MTD enantiomers. (S)-MTD is being developed as an antidepressant and is considered an N-methyl-D-aspartate receptor...
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Article
Association of locus coeruleus integrity with Braak stage and neuropsychiatric symptom severity in Alzheimer’s disease
The clinical and pathophysiological correlates of locus coeruleus (LC) degeneration in Alzheimer’s disease (AD) could be clarified using a method to index LC integrity in vivo, neuromelanin-sensitive MRI (NM-M...
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Article
Tau modification by the norepinephrine metabolite DOPEGAL stimulates its pathology and propagation
The noradrenergic locus ceruleus (LC) is the first site of detectable tau pathology in Alzheimer’s disease (AD), but the mechanisms underlying the selective vulnerability of the LC in AD have not been complete...
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Article
Open AccessMetabolic effects of the schizophrenia-associated 3q29 deletion
The 1.6 Mb 3q29 deletion is associated with developmental and psychiatric phenotypes, including a 40-fold increased risk for schizophrenia. Reduced birth weight and a high prevalence of feeding disorders in pa...
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Article
RGS14 modulates locomotor behavior and ERK signaling induced by environmental novelty and cocaine within discrete limbic structures
In rodents, exposure to novel environments or psychostimulants promotes locomotion. Indeed, locomotor reactivity to novelty strongly predicts behavioral responses to psychostimulants in animal models of addict...
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Article
Co-released norepinephrine and galanin act on different timescales to promote stress-induced anxiety-like behavior
Both the noradrenergic and galaninergic systems have been implicated in stress-related neuropsychiatric disorders, and these two neuromodulators are co-released from the stress-responsive locus coeruleus (LC);...
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Article
ApoE4 inhibition of VMAT2 in the locus coeruleus exacerbates Tau pathology in Alzheimer’s disease
ApoE4 enhances Tau neurotoxicity and promotes the early onset of AD. Pretangle Tau in the noradrenergic locus coeruleus (LC) is the earliest detectable AD-like pathology in the human brain. However, a direct r...
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Article
Open AccessBehavioral changes and growth deficits in a CRISPR engineered mouse model of the schizophrenia-associated 3q29 deletion
The 3q29 deletion confers increased risk for neuropsychiatric phenotypes including intellectual disability, autism spectrum disorder, generalized anxiety disorder, and a >40-fold increased risk for schizophren...
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Article
Locus coeruleus: a new look at the blue spot
The locus coeruleus (LC), or ‘blue spot’, is a small nucleus located deep in the brainstem that provides the far-reaching noradrenergic neurotransmitter system of the brain. This phylogenetically conserved nuc...
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Article
Noradrenergic circuits in the forebrain control affective responses to novelty
In rodents, exposure to novel environments elicits initial anxiety-like behavior (neophobia) followed by intense exploration (neophilia) that gradually subsides as the environment becomes familiar. Thus, innat...
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Article
Stressing the potential of guanfacine as a treatment for cocaine use disorder
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Article
Central norepinephrine transmission is required for stress-induced repetitive behavior in two rodent models of obsessive-compulsive disorder
Obsessive-compulsive disorder (OCD) is characterized by repetitive behaviors exacerbated by stress. Many OCD patients do not respond to available pharmacotherapies, but neurosurgical ablation of the anterior c...
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Article
Elimination of galanin synthesis in noradrenergic neurons reduces galanin in select brain areas and promotes active co** behaviors
Accumulating evidence indicates that disruption of galanin signaling is associated with neuropsychiatric disease, but the precise functions of this neuropeptide remain largely unresolved due to lack of tools f...
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Article
Selective D2 and D3 receptor antagonists oppositely modulate cocaine responses in mice via distinct postsynaptic mechanisms in nucleus accumbens
The dopamine D3 receptor (D3R) has emerged as a promising pharmacotherapeutic target for the treatment of several diseases including schizophrenia, Parkinson’s disease, and substance use disorders. However, studi...
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Article
Chronic adolescent stress sex-specifically alters the hippocampal transcriptome in adulthood
Chronic adolescent stress alters behavior in a sex-specific manner at the end of adolescence and in adulthood. Although prolonged behavioral repercussions of chronic adolescent stress have been documented, the...
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Article
Open AccessThe DREADD agonist clozapine N-oxide (CNO) is reverse-metabolized to clozapine and produces clozapine-like interoceptive stimulus effects in rats and mice
Clozapine-N-oxide (CNO) has long been the ligand of choice for selectively activating Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). However, recent studies have challenged the long-held...
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Article
Effects of disulfiram on choice behavior in a rodent gambling task: association with catecholamine levels
Gambling disorder is a growing societal concern, as recognized by its recent classification as an addictive disorder in the DSM-5. Case reports have shown that disulfiram reduces gambling-related behavior in h...
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Article
Open AccessLSD1 protects against hippocampal and cortical neurodegeneration
To investigate the mechanisms that maintain differentiated cells, here we inducibly delete the histone demethylase LSD1/KDM1A in adult mice. Loss of LSD1 leads to paralysis, along with widespread hippocampus a...
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Article
The effects of post-extinction exercise on cocaine-primed and stress-induced reinstatement of cocaine seeking in rats
Voluntary aerobic exercise has shown promise as a treatment for substance abuse, reducing relapse in cocaine-dependent people. Wheel running also attenuates drug-primed and cue-induced reinstatement of cocaine...
