ArticlePsychopharmacology2012
The effects of PRX-07034, a novel 5-HT6 antagonist, on cognitive flexibility and working memory in rats.
Article in Psychopharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 42 citations in OpenAlex.
- Serotonergic System Dysregulation in Alzheimer's Disease.ACS chemical neuroscience · 2026Review
- Recent advancements in pharmacological strategies to modulate energy balance for combating obesity.RSC medicinal chemistry · 2023Review
- Serotonin Receptors as Therapeutic Targets for Autism Spectrum Disorder Treatment.International journal of molecular sciences · 2022Review
- Modulating role of serotonergic signaling in sleep and memory.Pharmacological reports : PR · 2022Review
- Impact of specific serotonin receptor modulation on behavioral flexibility.Pharmacology, biochemistry, and behavior · 2021Review
- Progressive long-term spatial memory loss following repeat concussive and subconcussive brain injury in mice, associated with dorsal hippocampal neuron loss, microglial phenotype shift, and vascular abnormalities.The European journal of neuroscience · 2021Article
- NovelPharmaceuticals (Basel, Switzerland) · 2021Article
- Review
- Serotonin Type 6 and 7 Receptors as a Novel Therapeutic Target for the Treatment of Schizophrenia.Neuropsychiatric disease and treatment · 2020Review
- 5HT6 Antagonists in the Treatment of Alzheimer's Dementia: Current Progress.Neurology and therapy · 2018Review
- Alzheimer's disease drug development pipeline: 2018.Alzheimer's & dementia (New York, N. Y.) · 2018Article
- Cognitive flexibility impairment and reduced frontal cortex BDNF expression in the ouabain model of mania.Neuroscience · 2017Article
- BDNF regains function in hippocampal long-term potentiation deficits caused by diencephalic damage.Learning & memory (Cold Spring Harbor, N.Y.) · 2017Article
- Cognitive set shifting deficits and their relationship to repetitive behaviors in autism spectrum disorder.Journal of autism and developmental disorders · 2015Article
- Ongoing behavioral state information signaled in the lateral habenula guides choice flexibility in freely moving rats.Frontiers in behavioral neuroscience · 2015Article
- Contralateral disconnection of the rat prelimbic cortex and dorsomedial striatum impairs cue-guided behavioral switching.Learning & memory (Cold Spring Harbor, N.Y.) · 2014Article
- The prelimbic cortex and subthalamic nucleus contribute to cue-guided behavioral switching.Neurobiology of learning and memory · 2014Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleAccumulating evidence indicates that schizophrenia and autism spectrum disorder patients are marked by cognitive deficits in working memory and strategy switching. There is accumulating evidence that 5-hydroxytryptamine (5-HT)(6) receptors may serve as a useful target to improve cognitive functioning.
objectivesIn the present experiments, the novel 5-HT(6) antagonist, PRX-07034, was examined for its selectivity of the 5-HT(6) receptor, as well as its effect on delayed spontaneous alternation and strategy switching.
methodsThe binding affinity of PRX-07034 to the 5-HT(6) receptor, other 5-HT receptors, as well as other G-protein coupled receptors, ion channels, and transporters was evaluated. Cyclic AMP production was measured from transfected HEK-293 cells. In separate behavioral experiments, rats received different doses of PRX-07034 (0.1, 1, or 3 mg/kg, i.p.) 30 min prior to delayed spontaneous alternation testing or prior to the acquisition and switch phases in a place-response switch test.
resultsThe results indicated that PRX-07034 is both a potent (Ki = 4-8 nM) and highly selective 5-HT(6) receptor antagonist (≥100-fold selectivity for the 5-HT(6) receptor compared to 68 other GPCRs, ion channels, and transporters, except D(3) (Ki = 71 nM) and 5-HT(1B) (Ki = 260 nM) receptors. For cyclic AMP quantification, PRX-07034 demonstrated antagonist activity (IC(50) = 19 nM) without an effect on basal levels and did not show any agonist activity up to 10 μM. PRX-07034 at 1 and 3 mg/kg (but not 0.1 mg/kg) significantly enhanced delayed spontaneous alternation. The drug at 1 and 3 mg/kg also enhanced switching between a place and response strategy, but did not affect initial learning of either a place or response discrimination.
conclusionsThese findings demonstrate that PRX-07034 is a selective 5-HT(6) receptor antagonist that may represent a novel treatment for enhancing working memory and cognitive flexibility.
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