ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2014
Functional status of the serotonin 5-HT2C receptor (5-HT2CR) drives interlocked phenotypes that precipitate relapse-like behaviors in cocaine dependence.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 76 citations in OpenAlex.
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- The psychedelic (-)-2,5-dimethoxy-4-iodoamphetamine [(-)-DOI] demonstrates efficacy in reducing cocaine reward and motivation in male rats.Psychopharmacology · 2025Article
- Involvement of a stress-responsive orbito-striatal projection in impulsive action in male rats.The international journal of neuropsychopharmacology · 2025Article
- Effects of access condition on substance use disorder-like phenotypes in male and female rats self-administering MDPV or cocaine.Drug and alcohol dependence · 2024Article
- Effects of access condition on substance use disorder-like phenotypes in male and female rats self-administering MDPV or cocaine.bioRxiv : the preprint server for biology · 2024Article
- TNFR1 signaling converging on FGF14 controls neuronal hyperactivity and sickness behavior in experimental cerebral malaria.Journal of neuroinflammation · 2023Article
- Innate cocaine-seeking vulnerability arising from loss of serotonin-mediated aversive effects of cocaine in rats.Cell reports · 2023Article
- Evaluation of the 5-HTPharmacological reports : PR · 2023Article
- Fibroblast growth factor 13-mediated regulation of medium spiny neuron excitability and cocaine self-administration.Frontiers in neuroscience · 2023Article
- Role of neuropeptide neuromedin U in the nucleus accumbens shell in cocaine self-administration in male rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- A serotonergic biobehavioral signature differentiates cocaine use disorder participants administered mirtazapine.Translational psychiatry · 2022Article
- Heightened cocaine-seeking in male rats associates with a distinct transcriptomic profile in the medial prefrontal cortex.Frontiers in pharmacology · 2022Article
- The role of serotoninergic system in psychostimulant effects.Postepy psychiatrii neurologii · 2021Review
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
- Safety and Preliminary Efficacy of Lorcaserin for Cocaine Use Disorder: A Phase I Randomized Clinical Trial.Frontiers in psychiatry · 2021Article
- Discovery of 4-Phenylpiperidine-2-Carboxamide Analogues as Serotonin 5-HTJournal of medicinal chemistry · 2020Article
- Suppression of cocaine relapse-like behaviors upon pimavanserin and lorcaserin co-administration.Neuropharmacology · 2020Article
- Serotonin in Animal Cognition and Behavior.International journal of molecular sciences · 2020Review
- Lorcaserin Alters Serotonin and Noradrenaline Tissue Content and Their Interaction With Dopamine in the Rat Brain.Frontiers in pharmacology · 2020Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Relapse vulnerability in cocaine dependence is rooted in genetic and environmental determinants, and propelled by both impulsivity and the responsivity to cocaine-linked cues ('cue reactivity'). The serotonin (5-hydroxytryptamine, 5-HT) 5-HT2C receptor (5-HT2CR) within the medial prefrontal cortex (mPFC) is uniquely poised to serve as a strategic nexus to mechanistically control these behaviors. The 5-HT2CR functional capacity is regulated by a number of factors including availability of active membrane receptor pools, the composition of the 5-HT2CR macromolecular protein complex, and editing of the 5-HT2CR pre-mRNA. The one-choice serial reaction time (1-CSRT) task was used to identify impulsive action phenotypes in an outbred rat population before cocaine self-administration and assessment of cue reactivity in the form of lever presses reinforced by the cocaine-associated discrete cue complex during forced abstinence. The 1-CSRT task reliably and reproducibly identified high impulsive (HI) and low impulsive (LI) action phenotypes; HI action predicted high cue reactivity. Lower cortical 5-HT2CR membrane protein levels concomitant with higher levels of 5-HT2CR:postsynaptic density 95 complex distinguished HI rats from LI rats. The frequency of edited 5-HT2CR mRNA variants was elevated with the prediction that the protein population in HI rats favors those isoforms linked to reduced signaling capacity. Genetic loss of the mPFC 5-HT2CR induced aggregate impulsive action/cue reactivity, suggesting that depressed cortical 5-HT2CR tone confers vulnerability to these interlocked behaviors. Thus, impulsive action and cue reactivity appear to neuromechanistically overlap in rodents, with the 5-HT2CR functional status acting as a neural rheostat to regulate, in part, the intersection between these vulnerability behaviors.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.