5-HT2A and 5-HT2C receptor antagonists have opposing effects on a measure of impulsivity: interactions with global 5-HT depletion
PsychopharmacologyPublished 29 June 2004
Catharine A. Winstanley, David E. H. Theobald, Jeffrey W. Dalley, Jeffrey Glennon, Trevor W. Robbins
Citations326
SJR quartileQ1
SJR score1.16
SNIP0.97
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
Data support the view that serotonergic regulation of impulsive behaviour through different members of the 5-HT2 receptor family is functionally heterogeneous.
Abstract
These data support the view that serotonergic regulation of impulsive behaviour through different members of the 5-HT(2) receptor family is functionally heterogeneous. Although both 5-HT(2A) and 5-HT(2C) receptors participate in controlling this form of impulsive action, their relative contribution may depend on the endogenous state of the 5-HT system.
Keywords
MedicineNeuroscienceBiochemistry, Genetics and Molecular Biology
Elsevier eBooksThe Rat Brain in Stereotaxic Coordinates
52,250 Citations1982Paxinos, George, Watson, Charles
This paper presents a meta-analyses of the determinants of earthquake-triggered landsliding in the Czech Republic over a period of 18 months in order to establish a probabilistic framework for estimating the intensity of the earthquake.
NeuropharmacologyA review of central 5-HT receptors and their function
3,147 Citations1999Nicholas M. Barnes, Trevor Sharp
A number of 5-HT receptor ligands are currently utilised, or are in clinical development, to reduce the symptoms of CNS dysfunction and the functional responses attributed to each receptor in the brain are reviewed.
Brain ResearchIsolated removal of hypothalamic or other brain nuclei of the rat
1,435 Citations1973Miklós Palkovits
Life SciencesLow cerebrospinal fluid 5-hydroxyindoleacetic acid concentration differentiates impulsive from nonimpulsive violent behavior
1,316 Citations1983M. Linnoila, Matti Virkkunen +4 more
Of the groups studied, impulsive violent offenders who had attempted suicide had the lowest 5HIAA levels, which may be a marker of impulsivity rather than violence.
NeuropsychopharmacologyDissociable Deficits in the Decision-Making Cognition of Chronic Amphetamine Abusers, Opiate Abusers, Patients with Focal Damage to Prefrontal Cortex, and Tryptophan-Depleted Normal Volunteers Evidence for Monoaminergic Mechanisms
1,116 Citations1999Robert D. Rogers
It is suggested that chronic amphetamine abusers show similar decision-making deficits to those seen after focal damage to orbitofrontal PFC, which may reflect altered neuromodulation of the orbitof prefrontal PFC and interconnected limbic-striatal systems by both the ascending 5-HT and mesocortical dopamine projections.
Behavioral and Brain SciencesReconciling the role of central serotonin neurons in human and animal behavior
1,012 Citations1986Philippe Soubrié
Whether anxiety reduction or increased impulsivity is more likely to account for animal behavioral changes associated with decreased serotonergic transmission is investigated, as well as the effects of manipulating central serotonin in experimental anxiety paradigms in animals (punishment, extinction, novelty).
Experimental NeurologyLimbic lesions and the problem of stimulus—Reinforcement associations
871 Citations1972BH Jones, Mortimer Mishkin
Only the impairment produced by the TPA lesion was consistent with a difficulty in the formation of such associations, an interpretation which is strengthened by a consideration of the gross behavioral abnormalities that have been described repeatedly following this same lesion.
Behavioural Brain ResearchEffects of lesions to ascending noradrenergic neurones on performance of a 5-choice serial reaction task in rats; implications for theories of dorsal noradrenergic bundle function based on selective attention and arousal
731 Citations1983Mirjana Carli, Trevor W. Robbins +2 more
Although intense white noise failed to produce differential impairments when presented simultaneously with the visual discriminanda, the DNAB lesion significantly impaired accuracy when the noise was presented immediately prior to, but not overlapping, the onset of the visual stimuli.
Journal of NeuroscienceDissociable Contributions of the Orbitofrontal and Infralimbic Cortex to Pavlovian Autoshaping and Discrimination Reversal Learning: Further Evidence for the Functional Heterogeneity of the Rodent Frontal Cortex
552 Citations2003Yogita Chudasama, Trevor W. Robbins
Two types of dissociation are suggested between the effects of OFC and ILC lesions: (1) OFC lesions impaired the learning processes implicated in pavlovian autoshaping but not instrumental simultaneous discrimination learning, whereas I LC lesions were unimpaired at autoshaped and their reversal learning deficit did not reflect perseveration, and (2) OfC lesions induced perseverative responding in reversal learning but did not disinhibit responses to pavlovia CS-.
Journal of NeuroscienceEnhanced and Impaired Attentional Performance After Infusion of D1 Dopaminergic Receptor Agents into Rat Prefrontal Cortex
551 Citations2000Sylvie Granon, Filippo Passetti +4 more
The results provide apparently the first demonstration of enhanced cognitive function after local administration of a D1 receptor agonist to the mPFC and suggest dissociable roles of D1 and D2 DA receptors of themPFC in modulating attentional function.
Behavioural Brain ResearchDissociable aspects of performance on the 5-choice serial reaction time task following lesions of the dorsal anterior cingulate, infralimbic and orbitofrontal cortex in the rat: differential effects on selectivity, impulsivity and compulsivity
534 Citations2003Yogita Chudasama, Filippo Passetti +4 more
Different behavioural effects following dorsal and ventral lesions of the rodent frontal cortex signifies the integrity of the frontal cortex in multiple executive mechanisms that work independently and complementarily by which performance is optimized.
NeuropharmacologySB 242084, a Selective and Brain Penetrant 5-HT 2C Receptor Antagonist
523 Citations1997G.A. Kennett, Martyn Wood +12 more
The results suggest that SB 242084 is the first reported selective potent and brain penetrant 5- HT2C receptor antagonist and has anxiolytic-like activity, but does not possess either proconvulsant or hyperphagic properties which are characteristic of mutant mice lacking the 5-HT2C receptors.
Journal of NeuroscienceControl of Dorsal Raphe Serotonergic Neurons by the Medial Prefrontal Cortex: Involvement of Serotonin-1A, GABA<sub>A</sub>, and Glutamate Receptors
491 Citations2001Pau Celada, M. Victoria Puig +3 more
The results indicate the existence of a complex regulation of DR 5-HT neurons by mPFC afferents, and ascending serotonergic pathways may control the activity of this descending pathway by acting on postsynaptic 5- HT1A receptors.
PsychopharmacologyCentral 5-HT depletion enhances impulsive responding without affecting the accuracy of attentional performance: interactions with dopaminergic mechanisms
456 Citations1997Amanda Harrison, Barry J. Everitt +1 more
The results suggest that central 5-HT depletion results in impulsive, fast responding, which nevertheless does not impair accuracy of visual discrimination performance, and may be mediated by altered 5- HT-dopamine interactions.
NeuropsychopharmacologyFractionating Impulsivity: Contrasting Effects of Central 5-HT Depletion on Different Measures of Impulsive Behavior
380 Citations2004Catharine A. Winstanley, Jeffrey W. Dalley +2 more
Not all measures of impulsivity appear to be uniformly affected by 5-HT depletion, or correlate with each other, supporting the suggestion that impulsivity is not a unitary construct.
NeuropsychopharmacologyEffects of THC on Behavioral Measures of Impulsivity in Humans
371 Citations2003J. M. McDonald, L Schleifer +2 more
The results suggest that THC may increase certain forms of impulsive behavior while not affecting other impulsive behaviors, and the dissociations between the four measures of impulsivity suggest that impulsivity is an assemblage of distinct components rather than a unitary process.
Journal of Pharmacology and Experimental TherapeuticsPreclinical characterization of the potential of the putative atypical antipsychotic MDL 100,907 as a potent 5-HT2A antagonist with a favorable CNS safety profile.
358 Citations1996John H. Kehne, B M Baron +13 more
Preclinical data indicate that MDL 100,907 is a potent and selective ligand at the 5-HT2A receptor and selectivity as a potential antipsychotic in that it lacked consistent activity in selected rodent models of anticonvulsant, antidepressant, analgesic, or anxiolytic activity.
SynapseSerotonin2C receptors tonically suppress the activity of mesocortical dopaminergic and adrenergic, but not serotonergic, pathways: A combined dialysis and electrophysiological analysis in the rat
334 Citations2000Alain P. Gobert, Jean‐Michel Rivet +7 more
5‐HT2C receptors exert a tonic, suppressive influence on the activity of mesocortical — as well as mesolimbic and nigrostriatal — dopaminergic pathways, likely via indirect actions expressed at the level of their cell bodies.
NeuroreportOrbitofrontal lesions in rats impair reversal but not acquisition of go, no-go odor discriminations
330 Citations2002Geoffrey Schoenbaum, Summer L. Nugent +2 more
It is found that rats with lesions of the orbitofrontal cortex acquired novel discrimination problems at the same rate as controls andImpairments were evident in lesioned rats when the response contingencies of the odors in the discrimination problem were reversed.
Behavioural Brain ResearchEffects of 6-hydroxydopamine lesions of the nucleus accumbens septi on performance of a 5-choice serial reaction time task in rats: Implications for theories of selective attention and arousal
318 Citations1989Belinda J. Cole, Trevor W. Robbins
The lesion transiently attenuated both the speed and impulsivity of responding on the baseline schedule, but did not affect discriminative accuracy, supporting theories of a division of arousal-type processes.
NeuropharmacologySerotonin (5-HT)2C receptors tonically inhibit dopamine (DA) and noradrenaline (NA), but not 5-HT, release in the frontal cortex in vivo
282 Citations1998Mark J. Millan, Anne Dekeyne +1 more
The data suggest that 5-HT2C receptors exert a tonic, inhibitory influence upon frontocortical dopaminergic and adrenergic, but not serotonergic, transmission.
NeuropsychopharmacologyDeficits in Impulse Control Associated with Tonically-elevated Serotonergic Function in Rat Prefrontal Cortex
273 Citations2002Jeff Dalley
Elevated 5-HT release in the prefrontal cortex of rats during performance of a visual attentional task may underlie deficits in impulse control on this task, and DA dysfunction in this region may be another, possibly independent, trait marker of impulsivity.
PsychopharmacologyGlobal 5-HT depletion attenuates the ability of amphetamine to decrease impulsive choice on a delay-discounting task in rats
258 Citations2003Catharine A. Winstanley, Jeffrey W. Dalley +2 more
The ability of amphetamine to decrease impulsivity is not solely due to its effects on dopaminergic systems, but may also depend on serotonergic neurotransmission.
Journal of Biological ChemistryConstitutively active 5-hydroxytryptamine2C receptors reveal novel inverse agonist activity of receptor ligands.
257 Citations1994E L Barker, Ryan S. Westphal +2 more
Evidence is provided that constitutively active 5-HT2C receptors are biologically significant and the functionally distinct properties of inverse agonists and neutral antagonists may elucidate the mechanisms controlling basal receptor activity states and lead to novel approaches in the development of therapeutic agents.
NeuropsychopharmacologyDifferential Effects of the 5-HT2A Receptor Antagonist M100,907 and the 5-HT2C Receptor Antagonist SB242,084 on Cocaine-induced Locomotor Activity, Cocaine Self-administration and Cocaine-induced Reinstatement of Responding
250 Citations2002Paul Fletcher
The results indicate distinct, and in some cases opposite, effects of a 5-HT2A compared with a 5,HT2C receptor antagonist on various cocaine-mediated behavioral effects.
PsychopharmacologyAmphetamine impairs the discriminative performance of rats with dorsal noradrenergic bundle lesions on a 5-choice serial reaction time task: New evidence for central dopaminergic-noradrenergic interactions
239 Citations1987Belinda J. Cole, Trevor W. Robbins
Although DA and NA participate in qualitatively different behavioural processes, the effects of DNAB lesions on attentional processes depend on the level of DA activity within the nucleus accumbens, which is antagonised by systemic administration of the specific dopaminergic (DA) antagonist alpha-flupenthixol.
PsychopharmacologyIntra-prefrontal 8-OH-DPAT and M100907 improve visuospatial attention and decrease impulsivity on the five-choice serial reaction time task in rats
233 Citations2003Catharine A. Winstanley, Yogita Chudasama +4 more
Results indicate that modulation of 5-HT function within the mPFC via distinct receptors can enhance performance on the 5CSRT, and suggest a mechanism by which serotonergic agents improve cognitive function.
Trends in Pharmacological SciencesRole of 5-HT2C receptors in the control of central dopamine function
231 Citations2001Vincenzo Di Matteo, Antonio De Blasi +2 more
The role of 5-HT(2C) receptors in the control of brain DA function will be reviewed, and the search for new therapies for neuropsychiatric disorders, such as depression, schizophrenia and drug addiction, based on these findings will be discussed.
Life Sciences5-HT2A and 5-HT2C receptors and their atypical regulation properties
219 Citations2003Dirk Van Oekelen, Walter Luyten +1 more
The possible mechanisms of this paradoxical down-regulation are discussed, and a new hypothesis on possible heterologous regulation of 5-HT(2A) receptors is proposed.
British Journal of PharmacologyRole of the medial prefrontal cortex in 5‐HT<sub>1A</sub> receptor‐induced inhibition of 5‐HT neuronal activity in the rat
210 Citations1999Mihály Hajós, Éva Hajós‐Korcsok +1 more
Both transection of the frontal cortex as well as ablation of the medial region of the prefrontal cortex significantly attenuated the inhibition of 5‐ HT neurones induced by systemic administration of the 5‐HT1A receptor agonist, 8‐OH‐DPAT (0.5–16 μg kg−1, i.v.) in all neurones tested.
NeuroscienceSimultaneous quantification of serotonin, dopamine and noradrenaline levels in single frontal cortex dialysates of freely-moving rats reveals a complex pattern of reciprocal auto- and heteroreceptor-mediated control of release
203 Citations1998Alain P. Gobert, Jean‐Michel Rivet +4 more
There is a complex pattern of reciprocal autoreceptor and heteroceptor control of monoamine release in the frontal cortex of freely-moving rats using a novel and exceptionally sensitive method of high-performance liquid chromatography coupled to coulometric detection.
SynapsePeriodic maternal separation of neonatal rats produces region- and gender-specific effects on biogenic amine content in postmortem adult brain
198 Citations2001K. Matthews, Jeffrey W. Dalley +3 more
Evidence is provided that, in addition to the adult behavioral consequences, RMS leads to profound, region‐, and gender‐specific changes in brain monoamine content.
Brain ResearchBiochemical and electrophysiological evidence that RO 60-0175 inhibits mesolimbic dopaminergic function through serotonin2C receptors
182 Citations2000Vincenzo Di Matteo, Giuseppe Di Giovanni +2 more
Data confirm that central 5-HT system exerts an inhibitory control on the mesolimbic DA system and that 5- HT(2C) receptors are involved in this effect.
PsychopharmacologyThe 5-HT2A receptor antagonist M100,907 attenuates motor and 'impulsive-type' behaviours produced by NMDA receptor antagonism
178 Citations2003Guy A. Higgins, M Enderlin +2 more
The results suggest that 5-HT2A receptor antagonists may normalise certain 'impulsive' behaviours produced by NMDA receptor hypofunction, as well as attenuate the hyperlocomotion and stereotypy produced by dizocilpine.
Journal of Pharmacology and Experimental TherapeuticsInverse Agonist Activity of Atypical Antipsychotic Drugs at Human 5-Hydroxytryptamine2C Receptors
172 Citations2000Katharine Herrick‐Davis, Ellinor Grinde +1 more
The data suggest that 5-HT(2C) inverse agonist activity is associated with atypical antipsychotic drugs with moderate to high affinity for 5- HT( 2C) receptors, and imply that effects of atypICAL antipsychotics drugs on the 5-ht(2 C) receptor may play a role in their unique clinical properties.
NeuropharmacologySerotonin (5-HT)2A receptor activation enhances dialysate levels of dopamine and noradrenaline, but not 5-HT, in the frontal cortex of freely-moving rats
171 Citations1999Alain P. Gobert, Mark J. Millan
The 5-HT2 receptor agonist, DOI, dose-dependently increased dialysate levels of dopamine (DA) and noradrenaline (NA) in the frontal cortex (FCX) of freely-moving rats, but not5-HT, in the FCX in vivo, in contrast to a tonic, inhibitory influence of 5- HT2C receptors.
Behavioural Brain ResearchCentral serotonin depletion impairs both the acquisition and performance of a symmetrically reinforced go/no-go conditional visual discrimination
153 Citations1999Amanda Harrison, Barry J. Everitt +1 more
The results suggest that previous accounts of impulsive responding induced by 5-HT depletion fail to recognise the pervasive nature of this effect, which affects multiple behavioural indices of response disinhibition and can impede the acquisition and performance of discrimination tasks depending on their precise response requirements.
Journal of NeurochemistryBlockade of Striatal 5‐Hydroxytryptmine<sub>2</sub>Receptors Reduces the Increase in Extracellullar Concentrations of Dopamine Produced by the Amphhetamine analogue 3,4‐Methylenedioxymethamphetamine
130 Citations1994Christopher J. Schmidt, C. K. Sullivan +1 more
5‐HT2 receptors located in the striatum augment the release of dopamine produced by high doses of MDMA, and appear to be located on nondopaminergic elements of thestriatum.
Neuroscience LettersEffect of local injection of 8-OH-DPAT into the dorsal or median raphe nuclei on extracellular levels of serotonin in serotonergic projection areas in the rat brain
126 Citations1992Gilles Bonvento, B. Scatton +2 more
PsychopharmacologyThe 5-HT 1A receptor agonist 8-OH-DPAT reduces rats' accuracy of attentional performance and enhances impulsive responding in a five-choice serial reaction time task: role of presynaptic 5-HT 1A receptors
124 Citations2000Mirjana Carli, R. Samanin
The results suggest that stimulation of presynaptic 5-HT1A receptors is involved in the ability of 8-OH-DPAT to cause attentional dysfunction and enhance impulsivity while slowing of responding and increase in errors of omission mainly depend on stimulation of post-synaptic5-HT 1A receptors.
NeuropharmacologyActivation of 5-HT2A receptors impairs response control of rats in a five-choice serial reaction time task
106 Citations2000Tiina Koskinen, Sirja Ruotsalainen +5 more
The data suggest that the overactivation of 5-HT2A receptors impairs response control in a 5-CSRT task, whereas the overactivated 5- HT2C receptors can affect behavioral activity and/or arousal state of the animals for this food rewarded task.
Brain ResearchEffects of combined or separate 5,7-dihydroxytryptamine lesions of the dorsal and median raphe nuclei on responding maintained by a DRL 20s schedule of food reinforcement
86 Citations1995Paul Fletcher
It is suggested that destruction of 5-HT neurons arising from the median raphe is sufficient to disrupt behaviour maintained by a DRL 20s schedule, and that the behavioural changes observed may involve a deficit in timing.
Journal of Neural TransmissionRodent data and general hypothesis: antipsychotic action exerted through 5-HT2A receptor antagonism is dependent on increased serotonergic tone
83 Citations1998Peter Martin, Nicholas Waters +3 more
MK-801-induced hyperlocomotion is accompanied by an activation of, but is not fully dependent upon, brain serotonergic systems, an effect that is almost completely counterbalanced by a concomitant inhibitory impact on locomotion, mediated through stimulation of serotonin receptors other than 5-HT2A receptors.
SynapseEffect of destruction of serotonin neurons on basal and fenfluramine‐induced serotonin release in striatum
50 Citations1995Lynn G. Kirby, Deborah S. Kreiss +2 more
It is suggested that compensatory mechanisms may enable surviving 5‐ HT terminals to maintain basal 5‐HT levels in th striatum with as little as 5% of the terminals remaining, but those mechanisms are not sufficient to allow the damaged system to respond to a pharmacological challenge.
SynapseEffects of 5,7-dihydroxytryptamine depletion of tissue serotonin levels on extracellular serotonin in the striatum assessed with in vivo microdialysis: Relationship to behavior
49 Citations1999F. Scott Hall, A. Courtney DeVries +3 more
It was found that 5,7‐DHT depletion of striatal tissue levels of serotonin (5‐HT) does not diminish extracellular levels until substantial depletions occur, and this finding is similar to those observed after 6‐hydroxydopamine lesions of the brain dopamine systems.
Brain ResearchDifferential effects of serotonin (5-HT) lesions and synthesis blockade on neuropeptide-Y immunoreactivity and 5-HT1A, 5-HT1B/1D and 5-HT2A/2C receptor binding sites in the rat cerebral cortex
45 Citations1998Valérie Compan, Louis Ségu +2 more
Comparisons of the effects of serotonin (5-HT) synthesis blockade using chronic administration of p-chlorophenylalanine (PCPA) and 5,7-dihydroxytryptamine injections of variable volume suggest that different receptor subtypes might be involved in 5-HT-NPY relationships.