Ketamine reversed short-term memory impairment and depressive-like behavior in animal model of Parkinson's disease.
D. D. Vecchia, L. Kanazawa, E. Wendler, P. Hocayen, M. Vital, R. Takahashi, C. Cunha, E. Miyoshi, R. Andreatini
Brain Research Bulletin December 22, 2020 DOI: 10.1016/j.brainresbull.2020.12.011 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experiment Peer reviewed |
|---|---|
| Population | Male Wistar rats with bilateral 6-OHDA lesions of the substantia nigra pars compacta |
| Interventions | Ketamine Imipramine |
| Dose | 5, 10 and 15 mg/kg |
| Duration | 28 days |
| Topics | Esketamine Ketamine |
| Key findings | Ketamine reversed depressive-like behaviors and short-term memory impairment in rats with Parkinson's disease-like brain lesions. |
Abstract
The most common features of Parkinson's disease (PD) are motor impairments, but many patients also present depression and memory impairment. Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, has been shown to be effective in patients with treatment-resistant major depression. Thus, the present study evaluated the action of ketamine on memory impairment and depressive-like behavior in an animal model of PD. Male Wistar rats received a bilateral infusion of 6 μg/side 6-hydroxydopamine (6-OHDA) into the substantia nigra pars compacta (SNc). Short-term memory was evaluated by the social recognition test, and depressive-like behaviors were evaluated by the sucrose preference and forced swimming tests (FST). Drug treatments included vehicle (i.p., once a week); ketamine (5, 10 and 15 mg/kg, i.p., once a week); and imipramine (20 mg/kg, i.p., daily). The treatments were administered 21 days after the SNc lesion and lasted for 28 days. The SNc lesion impaired short-term social memory, and all ketamine doses reversed the memory impairment and anhedonia (reduction of sucrose preference) induced by 6-OHDA. In the FST, 6-OHDA increased immobility, and all doses of ketamine and imipramine reversed this effect. The anti-immobility effect of ketamine was associated with an increase in swimming but not in climbing, suggesting a serotonergic effect. Ketamine and imipramine did not reverse the 6-OHDA-induced reduction in tyrosine hydroxylase immunohistochemistry in the SNc. In conclusion, ketamine reversed depressive-like behaviors and short-term memory impairment in rats with SNc bilateral lesions, indicating a promising profile for its use in PD patients.
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
Cited by 8
- Psychedelic-inspired approaches for treating neurodegenerative disorders. Journal of Neurochemistry July 1, 2022
- Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms. Biomedicines October 9, 2024
- Exploring the multifaceted potential of (R)-ketamine beyond antidepressant applications. Frontiers in Pharmacology 2024
- Repurposing Ketamine in the Therapy of Depression and Depression-Related Disorders: Recent Advances and Future Potential. Aging and disease April 29, 2024
- Ketamine as a potential cognitive enhancer in neurological disorders: evidence from preclinical and clinical studies Frontiers in Neurology March 30, 2026
and 3 more in the library
Cites 14
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism American Journal of Psychiatry August 29, 2018
- BDNF Release Is Required for the Behavioral Actions of Ketamine The International Journal of Neuropsychopharmacology October 31, 2014
- Pathophysiology of depression and innovative treatments: remodeling glutamatergic synaptic connections Dialogues in Clinical Neuroscience March 31, 2014
- Role of hippocampal p11 in the sustained antidepressant effect of ketamine in the chronic unpredictable mild stress model Translational Psychiatry February 23, 2016
and 9 more in the library