Neuropsychopharmacology
August 29, 2026
Briana K Chen, Brenna L Williams, Anna Darling et al.
Brain-derived neurotrophic factor (BDNF) exon VI promoter is implicated in mediating activity-induced synthesis of hippocampal BDNF. BDNF is implicated in (R,S)-ketamine's antidepressant effects, but its role in (R,S)-ketamine-mediated prophylaxis is unknown. Using BDNF-e6 mice, in which promoter VI-driven BDNF production is disrupted, we tested its necessity for (R,S)-ketamine's prophylactic...
Alzheimer's Research & Therapy
July 15, 2025
Briana K Chen, Holly C Hunsberger, Alicia Whye et al.
Alzheimer's disease (AD) is the leading cause of dementia. There are limited approved medications that delay cognitive decline or lessen neuropsychiatric symptoms. Numerous clinical trials for AD using a single drug administration have failed to meet therapeutic endpoints, which is most likely due to the complexity of AD. A multimodal therapeutic intervention is more likely to improve symptoms...
Biological Psychiatry
July 7, 2025
Cory B Langreck, Briana K Chen, Victor M Luna et al.
9 citations
Contradictory evidence has emerged regarding the role of the mu opioid receptor (MOR) in the antidepressant actions of (R,S)-ketamine. Here, we used the long-acting MOR-selective antagonist methocinnamox (MCAM) to determine the contribution of MOR to the actions of (R,S)-ketamine and the more selective N-methyl-D-aspartate receptor (NMDAR) antagonist fluoroethylnormemantine (FENM) against...
Biological Psychiatry
May 1, 2025
Alessia Mastrodonato, Michelle Jin, Noelle Kee et al.
5 citations
We previously reported that a single injection of (R,S)-ketamine or its metabolite (2S,6S)-hydroxynorketamine (HNK) prior to stress attenuated learned fear. However, whether these drugs attenuate learned fear through divergent or convergent effects on neural activity remains to be determined. 129S6/SvEv male mice were injected with saline, (R,S)-ketamine, or (2S,6S)-HNK 1 week before a 3-shock...
Neuropsychopharmacology
April 22, 2025
Briana K Chen, Alicia Whye, Louise C Matthews et al.
2 citations
Serotonin (5-HT) receptors and N-methyl-D-aspartate receptors (NMDARs) have both been implicated in stress-induced psychiatric disorders. However, there is a paucity of studies evaluating the effectiveness of novel combinatorial pharmacological treatments to treat stress-related disorders. Here, we evaluated whether administration of combinatorial (R,S)-ketamine, an NMDAR antagonist and Food...
Neuropharmacology
November 1, 2024
Thi Mai Loan Nguyen, Jean-Philippe Guilloux, Céline Defaix et al.
3 citations
(R,S)-ketamine (ketamine) has rapid and sustained antidepressant (AD) efficacy at sub-anesthetic doses in depressed patients. A metabolite of ketamine, including (2R,6R)-hydroxynorketamine ((6)-HNKs) has been reported to exert antidepressant actions in rodent model of anxiety/depression. To further understand the specific role of ketamine's metabolism in the AD actions of the drug, we evaluated...
The International Journal of Neuropsychopharmacology
October 1, 2024
Nicholas E Bulthuis, Josephine C McGowan, Liliana R Ladner et al.
2 citations
Standard antidepressant treatments often take weeks to reach efficacy and are ineffective for many patients. (R,S)-ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been shown to be a rapid-acting antidepressant and to decrease depressive symptoms within hours of administration. While previous studies have shown the importance of the GluN2B subunit of the NMDA receptor on...
Neuropsychopharmacology
August 2018
Josephine C McGowan, Collin Hill, Alessia Mastrodonato et al.
Recently, we have shown that ketamine given prior to stress exposure protects against the development of depressive-like behavior in mice. These data suggest that it may be possible to prevent the induction of affective disorders before they develop by administering prophylactic pharmaceuticals, a relatively nascent and unexplored strategy for psychiatry. Here, we performed metabolomics...
Biological Psychiatry
February 23, 2018
Alessia Mastrodonato, Randy Martinez, Ina P. Pavlova et al.
BACKGROUND We previously reported that a single injection of ketamine prior to stress protects against the onset of depressive-like behavior and attenuates learned fear. However, the molecular pathways and brain circuits underlying ketamine-induced stress resilience are still largely unknown. METHODS Here, we tested if prophylactic ketamine administration altered neural activity in the...
Frontiers in Molecular Neuroscience
2018
Christina T LaGamma, William W Tang, Ashlea A Morgan et al.
Ketamine has been found to have rapid, long-lasting antidepressant effects in treatment-resistant (TR) patients with major depressive disorder (MDD). Recently, we have also shown that ketamine acts as a prophylactic to protect against the development of stress-induced depressive-like behavior in mice, indicating that a preventative treatment against mental illness using ketamine is possible....
Biological Psychiatry
May 4, 2015
Rebecca A Brachman, J. Mcgowan, Jennifer N. Perusini et al.
Background Stress exposure is one of the greatest risk factors for psychiatric illnesses like Major Depressive Disorder (MDD) and Post-Traumatic Stress Disorder (PTSD). However, not all individuals exposed to stress develop affective disorders. Stress resilience, the ability to experience stress without developing persistent psychopathology, varies from individual to individual. Enhancing...