E-6801, a 5-HT6 receptor agonist, improves recognition memory by combined modulation of cholinergic and glutamatergic neurotransmission in the rat

  title={E-6801, a 5-HT6 receptor agonist, improves recognition memory by combined modulation of cholinergic and glutamatergic neurotransmission in the rat},
  author={Ian Kendall and Helge A. Slotten and Xavier Codony and Javier Burgueño and Petrus J. Pauwels and Jos{\'e} Miguel Vela and Kevin C.F. Fone},
Rationale and objectivesIn rats, 5-hydroxytryptamine6 (5-HT6) receptor antagonists improve learning and memory, but the effects of agonists are poorly defined. This study investigated the effects of 5-HT6 receptor agonists and antagonists on a rodent model of recognition memory.MethodsSelective 5-HT6 receptor agonists and antagonists were administered either alone, after a scopolamine-induced impairment, or combined with sub-effective doses of the acetylcholinesterase inhibitor, donepezil, or… 
The 5-hydroxytryptamine (serotonin) receptor 6 agonist EMD 386088 ameliorates ketamine-induced deficits in attentional set shifting and novel object recognition, but not in the prepulse inhibition in rats
The beneficial effects of the 5-HT6 agonist in ameliorating some of the ketamine-induced deficits relevant to schizophrenia seem likely to represent a useful pharmacological approach to the treatment of cognitive disturbances observed in this disorder.
5-HT6 receptor agonist and antagonist modulates ICV-STZ-induced memory impairment in rats
Findings in this study support the therapeutic potential of 5-HT6 receptor ligands in the treatment of cognitive dysfunction and prevent ICV-STZ-induced memory impairment when assessed by behavioral tests.
Role of 5-HT6 receptor in conditioned learning and memory
The main aim of the current thesis was to determine the role of the 5-HT6 receptor in a conditioned emotion response (CER) task in rats and to analyse the intracellular mechanisms involved in the behavioural effects exerted following treatment with 5- HT6 receptor ligands by examining changes in hippocampal protein expression.
5-HT6 receptor agonism facilitates emotional learning
The results indicate antidepressant efficacy and facilitation of emotional learning by 5-HT6 receptor agonism via mechanisms that promote neuronal plasticity in caudate putamen, hippocampus, and PFC.
New procognitive enhancers acting at the histamine H3 and AMPA receptors reverse natural forgetting in mice: comparisons with donepezil and memantine in the object recognition task
It is shown that mice exhibit significant object recognition at short but not long retention intervals separating the familiarization and recognition phases, and S 38093 and S 47445, detected as positive controls in the object recognition task, are promising compounds for the treatment of amnesic syndromes.
Memory formation and memory alterations: 5-HT6 and 5-HT7 receptors, novel alternative
  • A. Meneses
  • Biology, Psychology
    Reviews in the neurosciences
  • 2014
Evidence suggests that both 5-HT7 receptor agonists and antagonists might have promnesic and anti-amnesic effects, which seem to be dependent on the basal level of performance, i.e., normal or impaired.


Reversal of a cholinergic-induced deficit in a rodent model of recognition memory by the selective 5-HT6 receptor antagonist, Ro 04-6790
This study demonstrates that acute administration of Ro 04-6790 reverses a cholinergic but not a dopaminergic deficit in a rodent model of recognition memory and provides further support for a role of the 5-HT6 receptor in the regulation of cognitive function.
The Selective 5-HT6 Receptor Antagonist Ro4368554 Restores Memory Performance in Cholinergic and Serotonergic Models of Memory Deficiency in the Rat
Although Ro4368554 did not improve a time-related retention deficit, it reversed a cholinergic and a serotonergic memory deficit, suggesting that both mechanisms may be involved in the facilitation of object memory by Ro4 368554 and, possibly, other 5-HT6 receptor antagonists.
Impact of regional 5-HT depletion on the cognitive enhancing effects of a typical 5-ht6 receptor antagonist, Ro 04-6790, in the Novel Object Discrimination task
The ability of Ro 04-6790 to prolong object recognition memory requires blockade of MR 5-HT function, and widespread LV or selective MR, but not DR lesions, abolished the ability to delay natural forgetting.
5-HT6 receptor antagonists enhance retention of a water maze task in the rat
It is demonstrated that systemic administration of SB-271046-A and SB-357134-A produces improvements in retention of a water maze task in the rat, which indicates that 5-HT6 receptor antagonism may be involved in cognitive function.
Pro-cognitive effects of 5-HT6 receptor antagonists in the social recognition procedure in rats: implication of the frontal cortex
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.
An Assessment of the Effects of 5-HT6 Receptor Antagonists in Rodent Models of Learning
The results of the experiments are not consistent with previous reports that suggested that 5HT6 antagonists might have therapeutic potential for cognitive disorders, and reference 5-HT6 receptor antagonists failed to demonstrate any significant effects suggestive of utility as cognition enhancing agents.