Pro-cognitive effects of 5-HT6 receptor antagonists in the social recognition procedure in rats: implication of the frontal cortex

Loiseau, Florence; Dekeyne, Anne; Millan, Mark J.

doi:10.1007/s00213-007-0934-5

Cited by 93 publications

(70 citation statements)

References 68 publications

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“…abolished both the WAY-181187-induced and the scopolamineinduced social recognition deficit, further reinforcing the notion that 5-HT 6 receptor blockade improves cognitive function by modulating central cholinergic tone. The site of action for these studies was confirmed as being within the frontal cortex (using bilateral direct injections of WAY-181187 and SB-271046), 24 a key area involved with modulating cognitive function in this social recognition paradigm and one in which 5-HT 6 receptor localization has been reported. SB-399885 (1-30 mg/kg, p.o.)…”

Section: Cognitive Enhancing and Behavioral Profiles Of 5-ht 6 Receptmentioning

confidence: 64%

“…24 When suboptimal doses of WAY-181187 and scopolamine were combined in this social memory paradigm, there was a synergistic shift toward a deficit, suggesting that tonic activation of the 5-HT 6 receptor can disrupt cognitive processes linked to reductions in cholinergic tone. Furthermore, SB-271046 (20 mg/kg, i.p.)…”

Section: Cognitive Enhancing and Behavioral Profiles Of 5-ht 6 Receptmentioning

confidence: 93%

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5-HT6 Receptor Antagonists as Novel Cognitive Enhancing Agents for Alzheimer's Disease

et al. 2008

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Summary:Alzheimer's disease (AD) is a devastating neurological condition characterized by a progressive decline in cognitive performance accompanied by behavioral and psychological syndromes, such as depression and psychosis. The neurochemical correlates of these clinical manifestations now appear to involve dysfunctions of multiple neurotransmitter pathways. Because of the extensive serotonergic denervation that has been observed in the AD brain and the important role played by serotonin (5-HT) in both cognition and behavioral control, this neurotransmitter system has become a focus of concerted research efforts to identify new treatments for AD. 5-HT exerts its diverse physiological and pharmacological effects through actions on multiple receptor subtypes. One of the newest members of this family is the 5-HT 6 receptor, a subtype localized almost exclusively in the CNS, predominating in brain regions associated with cognition and behavior. With the subsequent development of selective 5-HT 6 receptor antagonists, preclinical studies in rodents and primates have elucidated the function of this receptor subtype in more detail. It is increasingly clear that blockade of 5-HT 6 receptors leads to an improvement of cognitive performance in a wide variety of learning and memory paradigms and also results in anxiolytic and antidepressant-like activity. These actions are largely underpinned by enhancements of cholinergic, glutamatergic, noradrenergic, and dopaminergic neurotransmission, together with learning-associated neuronal remodeling. A preliminary report that the cognitive enhancing properties of a 5-HT 6 receptor antagonist (namely, SB-742457) extends into AD sufferers further highlights the therapeutic promise of this mechanistic approach.

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Section: Cognitive Enhancing and Behavioral Profiles Of 5-ht 6 Receptmentioning

confidence: 64%

Section: Cognitive Enhancing and Behavioral Profiles Of 5-ht 6 Receptmentioning

confidence: 93%

5-HT6 Receptor Antagonists as Novel Cognitive Enhancing Agents for Alzheimer's Disease

et al. 2008

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“…Furthermore, 5-HT 6 R activates mTOR Complex 1 (mTORC1) in the prefrontal cortex, which is related to cognitive deficits, 2 and the receptor constitutively activates Cdk5 to control cortical neurons migration and promote neurite growth. 3 Blockade of 5-HT 6 R enhances cognitive performance in a broad range of tasks in rodents, 4,5 and phase II clinical studies have demonstrated efficacy of 5-HT 6 R antagonists (Iladopirdine = LuAE58054, SB742457, and AVN-211, Figure 1) in conjunction with donepezil in mild-to-moderate AD patients.…”

Section: T He Most Devastating Neurodegenerative Form Of Dementia Ismentioning

confidence: 99%

N1-Azinylsulfonyl-1H-indoles: 5-HT6 Receptor Antagonists with Procognitive and Antidepressant-Like Properties

Zajdel¹,

Marciniec

Satała³

et al. 2016

ACS Med. Chem. Lett.

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A series of N1-azinylsulfonyl-3-(1,2,3,6,tetrahyrdopyridin-4-yl)-1H-indole derivatives was designed to obtain highly potent 5-HT 6 receptor ligands. The study allowed for the identification of 25 (4-{[5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indol-1-yl]sulfonyl}isoquinoline), a potent and selective 5-HT 6 receptor antagonist. The selected compound, was evaluated in vivo in a novel object recognition (NOR) and forced swim (FST) tests in rats, demonstrating distinct pro-cognitive and antidepressant-like properties (MED = 1 mg/kg and 0.1 mg/kg, i.p., respectively). Compound SB-742457, used as comparator, reversed memory deficits in NOR task in similar doses, while in FST it was active in 10−30-fold higher dose (3 mg/kg). In contrast to SB-742457, which was active in Vogel test (MED = 3 mg/kg), compound 25 displayed no anxiolytic activity.

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“…Acetylcholine has been shown to play a key role in social recognition. Systemic administration of the partial muscarinic cholinergic agonist arecoline or the antagonist scopolamine has been shown to decrease or increase social recognition, respectively (Letty et al, 1997;Millan et al, 2007;Loiseau et al, 2008). Much less is known about the specific involvement of norepinephrine (NE) and, notably, dopamine (DA) and serotonin (5-HT) in social memory.…”

Section: Oxytocin and Social Recognitionmentioning

confidence: 99%

“…Finally, evidence of a role for the serotonergic system has also been observed. The 5-HT 4 and 5-HT 6 receptors have been implicated in social recognition, with the frontal cortex playing a key role in the mediation of these effects (Letty et al, 1997;Loiseau et al, 2008).…”

Section: Oxytocin and Social Recognitionmentioning

confidence: 99%

Social memories in rodents: Methods, mechanisms and modulation by stress

Kooij

Sandi

2012

Neuroscience & Biobehavioral Reviews

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a b s t r a c tIntact social memory forms the basis of meaningful interactions between individuals. Many factors can modulate the quality of social memory, and these have been studied in detail in rodents. Social memory, however, cannot be considered a single entity. The term social memory reflects different processes, such as social recognition of a novel conspecific individual and social learning (or 'learning from others'). This review summarizes the findings obtained with behavioral paradigms that were developed for the study of memory formation by social recognition and social learning. In particular, we focus on studies that include tests for social habituation/discrimination paradigms, tests for memory of a previously established social hierarchy and the social transmission of the food preference test. The role of individual differences and the main neurobiological mechanisms (i.e., the brain regions and neurochemical systems involved) that have been implicated in each of these types of social-related memories are reviewed. In addition, we address the key modulatory influence of stress on the formation of these types of memories; discussing the contribution of central (corticotropin-releasing factor, CRF) and peripheral (glucocorticoids) stress systems and their interactions with the social neuropeptide systems. Overall, we present here a general overview of the current state of a thriving research area within the field of social neuroscience.

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Pro-cognitive effects of 5-HT6 receptor antagonists in the social recognition procedure in rats: implication of the frontal cortex

Abstract: These results indicate that 5-HT6 receptors modulate social recognition by actions in the FCX and underpin their pertinence as targets for the treatment of psychiatric disorders in which cognitive function is compromised.

Cited by 93 publications

References 68 publications

5-HT6 Receptor Antagonists as Novel Cognitive Enhancing Agents for Alzheimer's Disease

5-HT6 Receptor Antagonists as Novel Cognitive Enhancing Agents for Alzheimer's Disease

N1-Azinylsulfonyl-1H-indoles: 5-HT6 Receptor Antagonists with Procognitive and Antidepressant-Like Properties

Social memories in rodents: Methods, mechanisms and modulation by stress

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