The effects of ketamine on sexual behavior, anxiety, and locomotion in female rats

Guarraci, Fay A.; Gonzalez, Chantal M.F.; Lucero, Devon; Womble, Paige D.; Abdel-Rahim, Heba; DeVore, Jennie; Kunkel, Marcela Nicole; Quadlander, Emma; Stinnett, Morgan; Boyette-Davis, Jessica A.

doi:10.1016/j.pbb.2017.12.004

Cited by 16 publications

(4 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is in line with investigations of repeated ketamine administration revealing opposite behavioral effects in female and male mice, indicated by anxiogenic effect exertion in the open field, a test for state anxiety, in females [ 16 ]. In contrast, it had been shown that female rats did not display higher state anxiety levels in the elevated plus maze test following repeated administration of ketamine [ 42 ]. For α 2 -adrenoceptor-agonists, anxiolytic properties were described [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of repeated anesthesia with ketamine and xylazine on the well-being of C57BL/6JRj mice

et al. 2018

View full text Add to dashboard Cite

Within the scope of the 3Rs of Russel and Burch, the number of laboratory animals can be reduced by repeated use of an animal. This strategy only becomes relevant, if the total amount of pain, distress or harm the individual animal experiences does not exceed the severity of a single manipulation. For example, when using imaging techniques, an animal can be examined several times during a study, but it has to be anesthetized each time imaging is performed. The severity of anesthesia is thought to be mild according to the Directive 2010/63/EU. However, the Directive does not differentiate between single and repeated anesthesia, although repeated anesthesia may have a greater impact on well-being. Hence, we compared the impact of single and repeated anesthesia (six times at an interval of three to four days) by injection of ketamine and xylazine (KX) on the well-being of adult female and male C57BL/6JRj mice. After anesthesia, well-being of mice was assessed according to a protocol for systematic assessment of well-being including nesting, the Mouse Grimace Scale (MGS), a test for trait anxiety, home cage activity, and the rotarod test for motor activity, food intake, and body weight, as well as corticosterone (metabolite) analysis. Repeated anesthesia increased the MGS in mice of both sexes and caused short-term effects on well-being of female mice in the immediate post-anesthetic period, indicated by longer lasting effects on trait anxiety-related behavior. However, corticosterone metabolite concentrations suggested that mice habituated to the stress induced by repeated KX administration. Hence, the mildly negative effects on well-being of repeated KX anesthesia do not seem to accumulate over time using the respective regimen. However, further observations for severity classification are warranted in order to more specifically determine the duration of mild distress and trait anxiety.

show abstract

Section: Discussionmentioning

confidence: 99%

Impact of repeated anesthesia with ketamine and xylazine on the well-being of C57BL/6JRj mice

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Both the open field test and tail suspension test have long been used to determine animals’ anxiety- and depression-like behaviors, respectively, in rodents ( Seibenhener and Wooten, 2015 ; Ueno et al, 2022 ). Specifically, the open field test has been widely used to measure the ketamine effects on anxiety-like behavior in rodents ( Guarraci et al, 2018 ; Pitsikas et al, 2019 ; Shin et al, 2019 ; Akillioglu and Karadepe, 2021 ; Yang et al, 2022 ; Acevedo et al, 2023 ). We thus measured locomotor activity and anxiety-like behavior using the open field test as carried out previously ( Shou et al, 2019 ).…”

Section: Methodsmentioning

confidence: 99%

Ketamine’s rapid antidepressant effects are mediated by Ca2+-permeable AMPA receptors

Zaytseva

Bouckova

Wiles

et al. 2023

eLife

View full text Add to dashboard Cite

Ketamine is shown to enhance excitatory synaptic drive in multiple brain areas, which is presumed to underlie its rapid antidepressant effects. Moreover, ketamine's therapeutic actions are likely mediated by enhancing neuronal Ca2+ signaling. However, ketamine is a noncompetitive NMDA receptor (NMDAR) antagonist that reduces excitatory synaptic transmission and postsynaptic Ca2+ signaling. Thus, it is a puzzling question how ketamine enhances glutamatergic and Ca2+ activity in neurons to induce rapid antidepressant effects while blocking NMDARs in the hippocampus. Here, we find that ketamine treatment in cultured mouse hippocampal neurons significantly reduces Ca2+ and calcineurin activity to elevate AMPA receptor (AMPAR) subunit GluA1 phosphorylation. This phosphorylation ultimately leads to the expression of Ca2+-Permeable, GluA2-lacking, and GluA1-containing AMPARs (CP-AMPARs). The ketamine-induced expression of CP-AMPARs enhances glutamatergic activity and glutamate receptor plasticity in cultured hippocampal neurons. Moreover, when a sub-anesthetic dose of ketamine is given to mice, it increases synaptic GluA1 levels, but not GluA2, and GluA1 phosphorylation in the hippocampus within one hour after treatment. These changes are likely mediated by ketamine-induced reduction of calcineurin activity in the hippocampus. Using the open field and tail suspension tests, we demonstrate that a low dose of ketamine rapidly reduces anxiety-like and depression-like behaviors in both male and female mice. However, when in vivo treatment of a CP-AMPAR antagonist abolishes the ketamine's effects on animals' behaviors. We thus discover that ketamine at the low dose promotes the expression of CP-AMPARs via reduction of calcineurin activity, which in turn enhances synaptic strength to induce rapid antidepressant actions.

show abstract

“…More often than not, we see the pattern with two or three of these behaviors affected. For instance, ketamine, at doses comparable to what is being used off-label to treat depression, increased time spent with a male rat during a partner-preference test and decreased the likelihood of leaving the male after sexual stimulation (Guarraci et al, 2018). In addition to pharmacological studies, we have also observed this pattern of enhanced motivation to mate under other conditions.…”

Section: Indications Of Motivationmentioning

confidence: 99%

“What a Girl Wants”: What Can We Learn From Animal Models of Female Sexual Motivation?

Guarraci

Frohardt

2019

Front. Behav. Neurosci.

Self Cite

View full text Add to dashboard Cite

Sexual motivation is notably different than other motivations such as hunger and thirst, because it lacks homeostatic drive. Sexual motivation poses no threat to physical well-being; individual survival is not at stake. Nevertheless, sexual motivation is a powerful drive and is critical for species survival. Understanding the complexity of sexual motivation has the potential to advance our understanding of other motivations, even pathological motivations, such as those associated with substance abuse. The study of motivation that is unique to females has often been neglected. A number of paradigms have been developed to investigate female sexual motivation beyond measuring only the lordosis reflex. Lordosis is a reflexive posture displayed by female mammals in response to male sexual stimulation to facilitate intromission. The lordosis reflex is essential, but studying the drive to mate is compromised in the absence of robust lordosis. Therefore, appetitive measures of sexual behavior (e.g., preferences, solicitation behaviors) are more specific and more sensitive indicators of sexual motivation than lordosis alone. Paradigms designed to study female sexual motivation often provide a female subject with the choice to interact with a sexually vigorous male or either a non-sexual partner (i.e., female, castrated male) or to remain alone. The study of appetitive measures of sexual motivation has elucidated the role of hormones in female sexual motivation, as well as the underlying neural pathways. The present review describes methods for studying female rats to advance our understanding of sexual motivation and sexual dysfunction.

show abstract

The effects of ketamine on sexual behavior, anxiety, and locomotion in female rats

Cited by 16 publications

References 53 publications

Impact of repeated anesthesia with ketamine and xylazine on the well-being of C57BL/6JRj mice

Impact of repeated anesthesia with ketamine and xylazine on the well-being of C57BL/6JRj mice

Ketamine’s rapid antidepressant effects are mediated by Ca2+-permeable AMPA receptors

“What a Girl Wants”: What Can We Learn From Animal Models of Female Sexual Motivation?

Contact Info

Product

Resources

About