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Lessons learned from using fMRI in the early clinical development of a mu-opioid receptor antagonist for disorders of compulsive consumption
Functional magnetic resonance imaging (fMRI) has been widely used to gain a greater understanding of brain circuitry abnormalities in CNS disorders. fMRI has also been used to examine pharmacological modulatio...
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Article
Open AccessSafety, pharmacokinetics and exploratory pro-cognitive effects of HTL0018318, a selective M1 receptor agonist, in healthy younger adult and elderly subjects: a multiple ascending dose study
The cholinergic system and M1 receptor remain an important target for symptomatic treatment of cognitive dysfunction. The selective M1 receptor partial agonist HTL0018318 is under development for the symptomatic ...
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Article
Open AccessThe opioid receptor pharmacology of GSK1521498 compared to other ligands with differential effects on compulsive reward-related behaviours
The novel opioid receptor antagonist, GSK1421498, has been shown to attenuate reward-driven compulsive behaviours, such as stimulant drug seeking or binge eating, in animals and humans. Here, we report new dat...
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Article
Open AccessNeuroendocrine and sympathetic responses to an orexin receptor antagonist, SB-649868, and Alprazolam following insulin-induced hypoglycemia in humans
The orexin-hypocretin system is important for translating peripheral metabolic signals and central neuronal inputs to a diverse range of behaviors, from feeding, motivation and arousal, to sleep and wakefulnes...
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Impact of escitalopram on vagally mediated cardiovascular function in healthy participants: implications for understanding differential age-related, treatment emergent effects
Black box warnings for young adults under the age of 25 years indicate that antidepressants may increase risk of suicide. While underlying mechanisms for age-related treatment effects remain unclear, vagally m...
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Article
BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases
Scientific advancement in neuroscience has not been effectively translated into therapies for neurological diseases. In general, 'toxin reducing' approaches (f...
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Article
Effects of mu opioid receptor antagonism on cognition in obese binge-eating individuals
Translational research implicates the mu opioid neurochemical system in hedonic processing, but its role in dissociable high-level cognitive functions is not well understood. Binge-eating represents a useful m...
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Article
Chronic modulation of serotonergic neurotransmission with sertraline attenuates the loudness dependence of the auditory evoked potential in healthy participants
The loudness dependence of the auditory evoked potential (LDAEP) has been reported to be an effective non-invasive measure of central serotonergic neurotransmission. However, acute manipulations of the seroton...
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Article
Acute dopamine and/or serotonin depletion does not modulate mismatch negativity (MMN) in healthy human participants
Schizophrenia is commonly associated with impairments in pre-attentive change detection, as represented by reduced mismatch negativity (MMN). While the neurochemical basis of MMN has been linked to N-methyl-d-asp...
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Article
Evidence for modulation of facial emotional processing bias during emotional expression decoding by serotonergic and noradrenergic antidepressants: an event-related potential (ERP) study
Serotonergic (SSRI) and noradrenergic (NRI) antidepressants modulate biases in emotional processing such that perceptual bias is shifted away from negative and towards positive emotional material. However, the...
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Article
Acute high-dose glycine attenuates mismatch negativity (MMN) in healthy human controls
Schizophrenia is commonly associated with impairments in pre-attentive change detection as represented by reduced mismatch negativity (MMN). The neurochemical basis of MMN has been linked to N-methyl-d-aspartate ...
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Article
High-dose glycine inhibits the loudness dependence of the auditory evoked potential (LDAEP) in healthy humans
The loudness dependence of the auditory evoked Potential (LDAEP) has been suggested to be a putative marker of central serotonin function, with reported abnormalities in clinical disorders presumed to reflect ...
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Article
Acute dopamine D1 and D2 receptor stimulation does not modulate mismatch negativity (MMN) in healthy human subjects
Schizophrenia is commonly associated with an impairment in pre-attentive change detection, as represented by reduced mismatch negativity (MMN), an auditory event related potential. While the neurochemical basi...
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Article
Dopamine receptor stimulation does not modulate the loudness dependence of the auditory evoked potential in humans
The Loudness Dependence of the Auditory Evoked Potential (LDAEP) has been suggested as a reliable measure of central serotonin function in humans; however, its specificity for the serotonin system remains a to...
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Article
Combined D1/D2 receptor stimulation under conditions of dopamine depletion impairs spatial working memory performance in humans
The mesocortical dopamine system is regarded as an important modulator of working memory. While it has been established that stimulation of the D1/D2 receptor in primates can improve spatial working memory perfor...