Sex-related differences in intravenous ketamine effects on dissociative stereotypy and antinociception in male and female rats.
Kennett D. Radford, Rina Y. Berman, Michael Zhang, T. J. Wu, Kwang-Hoon Choi
Pharmacology, Biochemistry, and Behavior September 22, 2020 DOI: 10.1016/j.pbb.2020.173042 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Adult male and female Sprague-Dawley rats, 10 weeks old |
| Intervention | Ketamine |
| Dose | 2 and 5 mg/kg |
| Duration | 10-min behavioral observation period; antinociception measured 10 min after observation |
| Measures | Dissociative stereotypy (head weaving, ataxia, circling), natural behaviors (horizontal activity, rearing, grooming), tail flick test |
| Topics | Esketamine Ketamine |
| Key findings | Intravenous ketamine increased dissociative stereotypy and horizontal activity and decreased rearing and grooming in both male and female rats, with sex differences at 5 mg/kg: greater ataxia in females and greater head weaving in males. Females showed greater head weaving during the low-estrogen diestrus phase. Both doses produced antinociception, and females were more sensitive to the low dose. The authors suggest intravenous ketamine may produce sex-related differences in dissociative behaviors and analgesia. |
Abstract
Ketamine, a multimodal dissociative anesthetic drug, is widely used to treat various conditions including acute pain and treatment-resistant depression. We previously reported that subanesthetic doses of intravenous (i.v.) ketamine produced transient dissociative stereotypy and antinociception in male rats. However, sex-related differences in the effects of i.v. ketamine on these measures are not well characterized. Adult male and female Sprague-Dawley rats (10 weeks old) received an i.v. bolus saline or ketamine (2 and 5 mg/kg), and dissociative stereotypy (head weaving, ataxia, and circling) and natural behaviors (horizontal activity, rearing, and grooming) were quantified over a 10-min period. Ten minutes after the behavioral observation, antinociception was measured using a tail flick test. The i.v. ketamine administration increased head weaving, ataxia, circling, and horizontal activity while decreasing rearing and grooming behaviors in male and female rats. Following 5 mg/kg ketamine administration, ataxia was greater in female rats, while head weaving was greater in male rats. Among the female rats, head weaving was greater in the low estrogen group (diestrus phase) as compared to the high estrogen group (proestrus/estrus phase). Ketamine doses (2 and 5 mg/kg) produced antinociception in male and female rats, and female rats were more sensitive to the antinociceptive effects of a low dose ketamine. The current findings suggest that i.v. ketamine administration, a clinically relevant route of administration, may produce sex-related differences in dissociative behaviors and analgesia between males and females.
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 10
- Sex difference alters the behavioral and cognitive performance in a rat model of schizophrenia induced by sub-chronic ketamine. Journal of Psychiatric Research October 1, 2024
- Pharmacokinetic, pharmacodynamic, and behavioural studies of deschloroketamine in Wistar rats. British Journal of Pharmacology 2022
- Behavioral sensitization and tolerance induced by repeated treatment with ketamine enantiomers in male Wistar rats. PLoS One 2024
- Effects of ketamine on fear memory extinction: a review of preclinical literature. Frontiers in Neuroscience 2025
- Ketamine and olanzapine alter behaviour and prefrontal-cortex BDNF differentially in male and female rats Scientific Reports August 23, 2025
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Cites 7
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- Association of Ketamine With Psychiatric Symptoms and Implications for Its Therapeutic Use and for Understanding Schizophrenia JAMA Network Open May 1, 2020
- A historical review of antidepressant effects of ketamine and its enantiomers. Pharmacology, Biochemistry, and Behavior February 5, 2020
- Role of kappa-opioid receptors in the effects of salvinorin A and ketamine on attention in rats. Psychopharmacology June 1, 2010
- Interaction of Sex and Age on the Dissociative Effects of Ketamine Action in Young Healthy Participants Frontiers in Neuroscience June 18, 2019
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