Decoding effects of psychoactive drugs in a high-dimensional space of eye movements in monkeys.
Xu Liu, Zhixian Cheng, He Lin, Jiangxiu Tan, Wenyao Chen, Yichuan Bao, Ying Liu, Lei Zhong, Yitian Yao, Liping Wang, Jijun Wang, Yong Gu
National Science Review November 1, 2023 DOI: 10.1093/nsr/nwad255 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal model, experimental study Peer reviewed |
|---|---|
| Sample size | 2 |
| Population | Two macaque monkeys |
| Interventions | Phencyclidine (PCP) Ketamine |
| Dose | PCP 3.0 mg/kg, ketamine 0.8 mg/kg |
| Duration | Daily injections |
| Topics | Ketamine |
| Keywords | Auditory evoked potential Monkey Oculomotor Phencyclidine Schizophrenia |
| Key findings | PCP and ketamine induce oculomotor and pupillary abnormalities similar to those seen in schizophrenia patients, and a machine-learning classifier can reliably distinguish drug-induced states across individuals. |
Abstract
Oculomotor behavior has been shown to be correlated with mental disorders in clinics, making it promising for disease diagnosis. Here we developed a thorough oculomotor test toolkit, involving saccade, smooth pursuit, and fixation, allowing the examination of multiple oculomotor parameters in monkey models induced by psychoactive drugs. Eye movements were recorded after daily injections of phencyclidine (PCP) (3.0 mg/kg), ketamine (0.8 mg/kg) or controlled saline in two macaque monkeys. Both drugs led to robust reduction in accuracy and increment in reaction time during high cognitive-demanding tasks. Saccades, smooth pursuit, and fixation stability were also significantly impaired. During fixation, the involuntary microsaccades exhibited increased amplitudes and were biased toward the lower visual field. Pupillary response was reduced during cognitive tasks. Both drugs also increased sensitivity to auditory cues as reflected in auditory evoked potentials (AEPs). Thus, our animal model induced by psychoactive drugs produced largely similar abnormalities to that in patients with schizophrenia. Importantly, a classifier based on dimension reduction and machine learning could reliably identify altered states induced by different drugs (PCP, ketamine and saline, accuracy = 93%). The high performance of the classifier was reserved even when data from one monkey were used for training and testing the other subject (averaged classification accuracy = 90%). Thus, despite heterogeneity in baseline oculomotor behavior between the two monkeys, our model allows data transferability across individuals, which could be beneficial for future evaluation of pharmaceutical or physical therapy validity.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cites 9
- Pharmacological and behavioral divergence of ketamine enantiomers: implications for abuse liability Molecular Psychiatry April 15, 2021
- Ketamine and depression: a narrative review Drug Design, Development and Therapy August 1, 2019
- Association of Ketamine With Psychiatric Symptoms and Implications for Its Therapeutic Use and for Understanding Schizophrenia JAMA Network Open May 1, 2020
- Reduction of dopamine D2/3 receptor binding in the striatum after a single administration of esketamine, but not R-ketamine: a PET study in conscious monkeys European Archives of Psychiatry and Clinical Neuroscience April 18, 2016
- The role of dissociation in ketamine's antidepressant effects. Nature Communications December 22, 2020
and 4 more in the library