Current Neuropharmacology
March 1, 2011
Yoko Hagino, Yukio Takamatsu, Hideko Yamamoto et al.
64 citations
MDMA increases extracellular dopamine and serotonin in the striatum and prefrontal cortex of mice. In mice lacking both dopamine and serotonin transporters, the dopamine increase in the striatum is absent, while the serotonin increase is greatly reduced. In the prefrontal cortex, MDMA raises dopamine levels regardless of transporter knockout. These findings confirm that MDMA acts on both the dopamine and serotonin transporters to elevate these neurotransmitters.
Journal of neuroscience research
January 1, 2024
Chitra Vinnakota, Anna Schroeder, Xin Du et al.
7 citations
Blocking NMDA receptors with drugs like PCP and ketamine causes psychosis-like symptoms in humans and hyperlocomotion in rodents. Mice lacking the GluN2D subunit of the NMDA receptor show reduced hyperlocomotion in response to these drugs, suggesting this subunit is key for that effect. This study tested male and female mice lacking GluN2D and found they also had blunted locomotor responses to PCP, S-ketamine, and R-norketamine, in both sexes. These knockout mice showed an anxious baseline, and the drugs had anxiolytic effects that varied by sex and genotype. S-ketamine disrupted spatial memory in females and object recognition in both sexes, regardless of genotype. The GluN2D subunit mediates sex-specific and drug-specific behavioral effects of NMDA receptor antagonists.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
May 15, 2025
Chitra Vinnakota, Matthew R Hudson, Kazutaka Ikeda et al.
6 citations
Working memory relies on synchronized brain oscillations involving interactions between pyramidal cells and GABAergic interneurons. NMDA receptor antagonists affect both oscillations and memory, but the link was unclear. In mice performing a touchscreen working memory task, phencyclidine (PCP) disrupted accuracy in wildtype but not GluN2D-knockout mice, indicating PCP's action requires the GluN2D subunit. MK-801, (S)-ketamine, and (R)-ketamine impaired accuracy in both genotypes. PCP increased baseline gamma power in the hippocampus only in wildtypes, while all drugs increased prefrontal gamma power. Low gamma activity during the memory maintenance phase rose when mice answered correctly, and this task-related increase was disrupted by all drugs. The GluN2D subunit mediates PCP's effects on hippocampal gamma and working memory.
Journal of pharmacological sciences
March 1, 2024
Aimi Yamagishi, Yuiko Ikekubo, Masayoshi Mishina et al.
6 citations
The ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) produces both immediate and lasting antidepressant-like effects in mice, while its stereoisomer (2S,6S)-HNK does not. The sustained effects depend on the GluN2D subunit of the NMDA receptor: they disappear in mice lacking this subunit, although the acute effects remain. In stressed wildtype mice, GluN2B protein expression decreases in the nucleus accumbens, but this decrease does not occur in GluN2D-knockout mice. These findings suggest that the GluN2D subunit, and possibly GluN2B, mediate the long-lasting antidepressant-like action of (2R,6R)-HNK.
Neuropsychopharmacology Reports
February 6, 2021
Yoko Hagino, F. Scott Hall, George R. Uhl et al.
3 citations
The hallucinogenic tryptamine analogue 5-MeO-DIPT decreases extracellular serotonin in the striatum but not in the prefrontal cortex of mice. In mice lacking the serotonin transporter, 5-MeO-DIPT does not affect serotonin levels, indicating its action depends on that transporter. When a 5-HT1A receptor antagonist is present, 5-MeO-DIPT substantially increases serotonin, suggesting the drug's serotonin reuptake inhibition is masked by its concurrent activation of 5-HT1A receptors. 5-MeO-DIPT also dose-dependently increases extracellular dopamine in the prefrontal cortex regardless of serotonin transporter presence, an effect not blocked by the 5-HT1A antagonist. Thus, 5-MeO-DIPT dually acts on the serotonin transporter and 5-HT1A receptors, limiting serotonin elevation while independently raising dopamine in the prefrontal cortex.
The International Journal of Neuropsychopharmacology
May 5, 2026
Hiroyuki Uchida, Gabriella Gobbi, Joseph Zohar et al.
Between 2013 and 2026, neuropsychopharmacology advanced from stagnation to momentum, producing several first-in-class treatments: rapid-acting drugs for treatment-resistant depression (intranasal esketamine), psychedelic-assisted therapy for PTSD and depression, neuroactive steroid GABA-A receptor positive allosteric modulators (brexanolone, zuranolone) for postpartum depression, non-dopaminergic muscarinic agonists (xanomeline-trospium) for schizophrenia, orexin receptor antagonists for insomnia, and anti-amyloid monoclonal antibodies (lecanemab, donanemab) for early Alzheimer's disease.