The 5-HT1A antagonist, WAY 100635, ameliorates the cognitive impairment induced by fornix transection in the marmoset

  title={The 5-HT1A antagonist, WAY 100635, ameliorates the cognitive impairment induced by fornix transection in the marmoset},
  author={J. A. Harder and Catherine J. Maclean and Rosalind M. Ridley and J. Tracy Alder and Paul T Francis},
Fornix transection in the marmoset produces a specific pattern of cognitive deficits, notably a lack of ability to recall visuospatial tasks learnt preoperatively, and a deficit in acquiring new visuospatial tasks following transection. Previous work has shown that this learning impairment can be ameliorated by cholinergic agonists, suggesting that it occurs as a consequence of destroying the cholinergic projection from the vertical limb of the diagonal band to the hippocampus which runs… 

Reversal of visual attention dysfunction after AMPA lesions of the nucleus basalis magnocellularis (NBM) by the cholinesterase inhibitor donepezil and by a 5-HT1A receptor antagonist WAY 100635

The attentional impairments induced due to cortical cholinergic dysfunction may be ameliorated by cholinerential treatments such as cholinesterase inhibitors and blockade of 5-HT1A receptors may be useful to treat some aspects of attentional dysfunction in AD.

Role of the serotonin 5-HT(2A) receptor in learning.

  • J. Harvey
  • Psychology, Biology
    Learning & memory
  • 2003
It was concluded that the 5-HT2A receptor demonstrates constitutive activity, and that variations in this activity can produce profound alterations in cognitive states.

Lecozotan (SRA-333): A Selective Serotonin 1A Receptor Antagonist That Enhances the Stimulated Release of Glutamate and Acetylcholine in the Hippocampus and Possesses Cognitive-Enhancing Properties

The heterosynaptic nature of the effects of lecozotan imbues this compound with a novel mechanism of action directed at the biochemical pathologies underlying cognitive loss in Alzheimer's disease.

The therapeutic effect of quetiapine on cognitive impairment associated with 5-HT1A presynaptic receptor involved schizophrenia.

The present study demonstrated the key role of presynaptic serotonin 1A receptors on the therapeutic effect of quetiapine on cognitive impairment associated with atypical antipsychotic drugs, and that protein kinase A activity in hippocampal cells is involved in the mechanism ofQuetiAPine's effect on cognitive impairing drugs.

Serotonin 5‐HT1A receptor blockade enhances Ca2+/calmodulin‐dependent protein kinase II function and membrane expression of AMPA receptor subunits in the rat hippocampus: implications for memory formation

It is suggested that blockade of hippocampal 5‐HT1A receptors favours molecular events critically involved in memory formation, and provides an in’vivo molecular basis for the proposed utility of 5‐ HT1A receptor antagonists in the treatment of cognitive disorders.

Correlating Efficacy in Rodent Cognition Models with in Vivo 5-Hydroxytryptamine1A Receptor Occupancy by a Novel Antagonist, (R)-N-(2-Methyl-(4-indolyl-1-piperazinyl)ethyl)-N-(2-pyridinyl)-cyclohexane Carboxamide (WAY-101405)

These studies demonstrate that WAY-101405 is a potent and selective, brain penetrant, orally bioavailable, silent 5-HT1A receptor “silent” antagonist that is effective in preclinical memory paradigms at doses where approximately 90% of the postsynaptic 5- HT1A receptors are occupied.

The 5‐HT1A receptor agonist 8‐OH‐DPAT prevents prefrontocortical glutamate and serotonin release in response to blockade of cortical NMDA receptors

Results show that the stimulation of cortical 5‐ HT1A receptors prevents the CPP‐evoked rise of extracellular GLU and 5‐HT and suggest that these effects may contribute to the ability of intracortical 8‐OH‐DPAT to counteract cognitive deficits caused by the blockade of NMDA receptors.

A positron emission tomography study of 5-hydroxytryptamine-1A receptors in Alzheimer disease.

  • K. LanctôtD. Hussey S. Kapur
  • Biology, Medicine
    The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry
  • 2007
Given the strategic role of these receptors, loss of right medial temporal 5-HT(1A) receptors might play an important role in AD symptomatology.

Novel antipsychotics activate recombinant human and native rat serotonin 5-HT1A receptors: affinity, efficacy and potential implications for treatment of schizophrenia.

The data indicate that aripiprazole has low efficacy and modest affinity at 5-HT1A receptors, whereas bifeprunox has low affinity but high efficacy, and SSR181507 has intermediate efficacy but high affinity, and is likely to have more prominent 5- HT1A receptor agonist properties.



Effects of excitotoxic lesions of the septum and vertical limb nucleus of the diagonal band of Broca on conditional visual discrimination: relationship between performance and choline acetyltransferase activity in the cingulate cortex

These experiments suggest that excitotoxic lesions of the septum/VDB produce deficits in conditional discrimination learning and performance, and that the integrity of the projection to the cingulate cortex is more crucial than that to the hippocampus in this effect.

Cholinergic neural transplants into hippocampus restore learning ability in monkeys with fornix transections

Bilateral transplantation of cholinergic-rich embryonic basal forebrain tissue into the hippocampus led to complete recovery from this specific learning impairment across a range of task difficulties.

Effects of Fornix Transection upon Associative Memory in Monkeys: Role of the Hippocampus in Learned Action

The results of seven experiments designed to elucidate further the effect of fornix tran section are incompatible with existing hypotheses of hippocampal function.

5.HT1 receptors in the vertebrate brain

The regional distribution of high affinity [33H]5-HT recognition sites in the brain of several vertebrates (pigeon, rat, mouse, guinea-pig, cat, dog, monkey and human) was analyzed using in vitro autoradiography and suggested that the majority of 5-HT1 sites belong to the 5- HT1D subtype in the pigeon brain.