I. Antidepressants and sexual behavior: Weekly ketamine injections increased sexual behavior initially in female and male rats.
F. Guarraci, Maryam Ali, Chantal M. F. Gonzalez, Devon Lucero, Larry Clemons, Lourdes K. Davis, Elizabeth L. Henneman, S. Odell, S. Meerts
Pharmacology, Biochemistry, and Behavior September 11, 2020 DOI: 10.1016/j.pbb.2020.173039 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Population | Female and male rats |
| Intervention | Ketamine |
| Dose | 10 mg/kg, i.p., once per week for four consecutive weeks |
| Duration | Four weekly injections per experiment, with a washout period before four additional weekly injections |
| Measures | Partner preference paradigm, elevated plus maze (EPM) |
| Topics | Esketamine Ketamine |
| Key findings | Weekly ketamine (10 mg/kg) did not produce sexual dysfunction in female or male rats and instead increased sexual motivation, with a robust initial response that diminished as animals gained sexual experience. Anxiety-like behavior on the elevated plus maze was minimal in both ketamine and saline groups. |
Abstract
The present study characterized the effects of weekly ketamine injections on sexual behavior and anxiety in female and male rats, using a dosing protocol that mimics human therapeutic treatment for depression. In Experiment 1A, ketamine (10 mg/kg, i.p.) or saline was injected once per week for four consecutive weeks. The partner preference paradigm was used to measure sexual motivation 30 min after each weekly injection. Briefly, subjects were first given a 10-min test during which they could choose to spend time in the vicinity of a sexually receptive female stimulus or a sexually experienced male stimulus, however physical contact was restricted (no-contact). Immediately after, subjects were given unrestricted access to the stimulus animals (contact). After a washout period, subjects received four additional weekly injections of ketamine or saline, and then were tested for anxiety-like behavior on the elevated plus maze (EPM) after the last injection (Experiment 1B). For Experiment 2, similar procedures were used to test the effects of weekly ketamine injections on sexual motivation (Experiment 2A) and anxiety (Experiment 2B) in male subjects. In female subjects, ketamine increased sexual motivation as measured by greater time spent with the male stimulus, decreased likelihood of leaving after receiving mounts, and shorter return latencies after receiving intromissions, when compared to saline controls. In male subjects, ketamine shortened latency to first mount and first intromission, as well as increased time spent with the female stimulus. Very little anxiety was observed in either group (ketamine or saline) of female or male subjects when tested on the EPM. In conclusion, even after four weeks of ketamine exposure, sexual dysfunction did not emerge in either females or males. In contrast, ketamine increased sexual motivation in both females and males, with an initial robust response. However, as both groups gained sexual experience, the impact of ketamine diminished.
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 13
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- 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 Journal of Neuroscience April 15, 1997
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders JAMA Psychiatry March 1, 2017
- Single, Repeated, and Maintenance Ketamine Infusions for Treatment-Resistant Depression: A Randomized Controlled Trial. American Journal of Psychiatry March 29, 2019
and 8 more in the library