The 5-HT1A antagonist, WAY 100 635, alleviates cognitive impairments induced by dizocilpine (MK-801) in monkeys

  title={The 5-HT1A antagonist, WAY 100 635, alleviates cognitive impairments induced by dizocilpine (MK-801) in monkeys},
  author={J. A. Harder and Rosalind M. Ridley},

Sensorimotor gating impairments induced by MK-801 treatment may be reduced by tolerance effect and by familiarization in monkeys

Results indicate that tolerance effect and familiarization with PPI test may reduce the sensorimotor gating deficits induced by MK-801 in monkeys, suggesting a drug-training interaction.


In vitro binding and intrinsic activity determinations demonstrated that lecozotan is a potent and selective 5-HT1A receptor antagonist and imbues this compound with a novel mechanism of action directed at the biochemical pathologies underlying cognitive loss in AD.

Exploring the Role of Acetylcholine in Primate Cognition Using Me20.4 IgG-Saporin

Studies with rats did not produce a correlation between the magnitude of cholinergic loss in the basal forebrain across various nonimmunotoxic lesion techniques and learning or performance impairments and the emergence of the “cholinergic hypothesis of geriatric memory dysfunction”.

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.

Subchronic Effects of Phencyclidine on Dopamine and Serotonin Receptors: Implications for Schizophrenia

It is suggested that downregulation of striatal D1 receptors and upregulation of cortical 5HT1A receptors may contribute to PCP-induced impairment of cognitive functions in rats, and a minimal role for these receptors in mediating subchronic actions of PCP in adult rats.

Cannabidiol Affects MK-801-Induced Changes in the PPI Learned Response of Capuchin Monkeys (Sapajus spp.)

The findings suggest that CBD’s reversal of the MK-801 effects on PPI is unlikely to stem from a direct involvement on sensorimotor mechanisms, but may possibly reflect its anxiolytic properties.



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

It is shown that fornix transection in the marmoset can be significantly alleviated by the 5-HT1A antagonist, which supports the suggestion that 5- HT1A projections are inhibitory on the same target cells for which cholinergic projections are excitatory.

Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5

It is reported that chronic intraventricular infusion of D, L-AP5 causes a selective impairment of place learning, which is highly sensitive to hippocampal damage7, without affecting visual discrimination learning,which is not8 and suggest that NMDA receptors are involved in spatial learning, and add support to the hypothesis that LTP is involved in some, but not all, forms of learning.

Learning impairments induced by glutamate blockade using dizocilpine (MK‐801) in monkeys

An effect of dizocilpine is found on acquisition and reversal of some types of cognitive task, at a dose which does not cause significant motor effects, which may be useful in understanding the contribution of glutamatergic dysfunction to cognitive decline in neurodegenerative disease, especially Alzheimer's disease.

The effect of dizocilpine (MK‐801) on conditional discrimination learning in the rat

Dizocilpine-treated rats were severely impaired on acquisition of a visuo-spatial task and were unable to learn the reversal of this task, which was larger than those found in comparable experiments using non-conditional tasks.

The effect of dizocilpine (MK‐801) on spatial and visual discrimination tasks in the rat

Dizocilpine had no effect on acquisition of the spatial task although, when this task was reversed, dizcilpine-treated rats took significantly more trials to reach criterion.

A critical evaluation of monkey models of amnesia and dementia

Physical basis of cognitive alterations in alzheimer's disease: Synapse loss is the major correlate of cognitive impairment

Both linear regressions and multivariate analyses correlating three global neuropsychological tests with a number of structural and neurochemical measurements performed on a prospective series of patients with Alzheimer's disease and 9 neuropathologically normal subjects reveal very powerful correlations with all three psychological assays.