Effects of age and sex on ketamine-induced hyperactivity in rats

Wilson, Christopher; Kercher, Melanie; Quinn, Belsida; Murphy, A.; Fiegel, Carey; McLaurin, Angel

doi:10.1016/j.physbeh.2007.02.010

Cited by 28 publications

(18 citation statements)

References 30 publications

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“…Values shown are means±SEM of four rats per group; the immunoblotting data are expressed as percentages of corresponding optical density (normalized to β-actin) in the vehicle control samples. **P<0.01 compared with TDS (−); ###P<0.001 compared with TDS-exposed group (ANOVA followed by Dunnett's t test) spontaneous locomotor activity in rats, which is consistent with earlier reports that ketamine does not affect locomotion in male adult Sprague-Dawley rats, over a large range of doses (e.g., 0-10 mg/kg) (Wilson et al 2007). These findings suggesting that the behavioral changes observed in this study were not due to a change in basal locomotor activity.…”

Section: Discussionsupporting

confidence: 88%

Anxiolytic effects of ketamine in animal models of posttraumatic stress disorder

Zhang¹,

Zhou

et al. 2014

Psychopharmacology

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This study investigated the effectiveness of ketamine, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, in alleviating the enhanced anxiety and fear response in both a mouse model of PTSD induced by inescapable electric foot shocks and a rat model of PTSD induced by a time-dependent sensitization (TDS) procedure. First, we evaluated the effect of ketamine on behavioral deficits in a mouse model of PTSD that consisted of foot shocks followed by three situational reminders. Our results showed that the aversive procedure induced several behavioral deficiencies, such as increased freezing behavior and anxiety, as well as reduced time spent in an aversive-like context, which were reversed by repeated treatment with ketamine. The effect of ketamine on behavioral changes after exposure to TDS was also investigated, and the levels of brain-derived neurotrophic factor (BDNF) in the hippocampus were measured. The results revealed that after TDS, the rats showed a significant increase in contextual freezing and a decrease in the percentage of time spent in and numbers of entries into open arms in the elevated plus maze test. As a positive control drug, sertraline (Ser, 15 mg/kg, i.g.), a selective serotonin reuptake inhibitor (SSRI) ameliorated these behavioral deficits. These behavioral effects were mimicked by chronic ketamine treatment. Furthermore, ketamine normalized the decreased BDNF level in the hippocampus in post-TDS rats. Taken together, these results suggest that ketamine exerts a therapeutic effect on PTSD that might be at least partially mediated by an influence on BDNF signaling in the hippocampus.

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Section: Discussionsupporting

confidence: 88%

Anxiolytic effects of ketamine in animal models of posttraumatic stress disorder

Zhang¹,

Zhou

et al. 2014

Psychopharmacology

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“…On the other hand, Wiley et al (2008) reported reduced stimulant effects of ketamine in adolescents, and Wilson et al (2007) reported negligible differences in ketamine-induced locomotor activity between adults and adolescents (both used a 10mg/kg dose). Consistent with our results and those of Parise et al (2013), Pesic and coworkers (2010), found that an acute dose of MK-801 (a highly potent and selective NMDA receptor antagonist), induced a greater increase in locomotor behavior in adolescents compared to adults.…”

Section: Discussionmentioning

confidence: 97%

Differences between adolescents and adults in the acute effects of PCP and ketamine and in sensitization following intermittent administration

Rocha

Hart

Trujillo

2017

Pharmacology Biochemistry and Behavior

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Adolescence is a phase of development during which many physiological and behavioral changes occur, including increased novelty seeking and risk taking. In humans, this is reflected in experimentation with drugs. Research demonstrates that drug use that begins during adolescence is more likely to lead to addiction than drug use that begins later in life. Despite this, relatively little is known of the effects of drugs in adolescence, and differences in response between adolescents and adults. PCP and ketamine are popular club drugs, both possessing rewarding properties that could lead to escalating use. Drug sensitization (or reverse tolerance), which refers to an increase in an effect of a drug following repeated use, has been linked with the development of drug cravings that is a hallmark of addiction. The current work investigated the acute response and the development of sensitization to PCP and ketamine in adolescent and adult rats. Periadolescent Sprague-Dawley rats (30 days or 38 days of age), and young adults (60 days of age) received PCP (6 mg/kg IP) or ketamine (20 mg/kg IP) once every three days, for a total of five drug injections. Adolescents and adults showed a stimulant response to the first injection of either drug, however the response was considerably greater in the youngest adolescents and lowest in the adults. With repeated administration, adults showed a robust escalation in activity that was indicative of the development of sensitization. Adolescents showed a flatter trajectory, with similar high levels of activity following an acute treatment and after five drug treatments. The results demonstrate important distinctions between adolescents and adults in the acute and repeated effects of PCP and ketamine.

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“…Female rats also exhibit elevated levels of locomotor activity after acute ketamine administration (Wiley et al 2011), and there is some evidence that the locomotor activating effects of ketamine are more pronounced in females than in males. Specifically, Wilson et al (2005; 2007) reported that a low dose of ketamine (10 mg/kg) increased the locomotion of both male and female rats on postnatal day (PD) 22, but stimulated the locomotor activity of only female rats during the early (PD 35) and late (PD 50) adolescent periods. To some extent the latter results are difficult to interpret because only a single low-dose of ketamine was used, and behavioral testing lasted for only 10 min.…”

Section: Introductionmentioning

confidence: 99%

Effects of ketamine on the unconditioned and conditioned locomotor activity of preadolescent and adolescent rats: impact of age, sex, and drug dose

et al. 2017

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Rationale Ketamine is used by preadolescent and adolescent humans for licit and illicit purposes. Objective The goal of the present study was to determine the effects of acute and repeated ketamine treatment on the unconditioned behaviors and conditioned locomotor activity of preadolescent and adolescent rats. Methods To assess unconditioned behaviors, female and male rats were injected with ketamine (5–40 mg/kg) and distance traveled was measured on PD 21–25 or PD 41–45. To assess conditioned activity, male and female rats were injected with saline or ketamine in either a novel test chamber or the home cage on PD 21–24 or PD 41–44. One day later, rats were injected with saline and conditioned activity was assessed. Results Ketamine produced a dose-dependent increase in the locomotor activity of preadolescent and adolescent rats. Preadolescent rats did not exhibit sex differences, but ketamine-induced locomotor activity was substantially stronger in adolescent females than males. Repeated ketamine treatment neither caused a day-dependent increase in locomotor activity nor produced conditioned activity in preadolescent or adolescent rats. Conclusions The activity-enhancing effects of ketamine are consistent with the actions of an indirect dopamine agonist, while the inability of ketamine to induce conditioned activity is unlike what is observed after repeated cocaine or amphetamine treatment. This dichotomy could be due to ketamine’s ability to both enhance DA neurotransmission and antagonize NMDA receptors. Additional research will be necessary to parse out the relative contributions of DA and NMDA system functioning when assessing the behavioral effects of ketamine during early ontogeny.

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Effects of age and sex on ketamine-induced hyperactivity in rats

Cited by 28 publications

References 30 publications

Anxiolytic effects of ketamine in animal models of posttraumatic stress disorder

Anxiolytic effects of ketamine in animal models of posttraumatic stress disorder

Differences between adolescents and adults in the acute effects of PCP and ketamine and in sensitization following intermittent administration

Effects of ketamine on the unconditioned and conditioned locomotor activity of preadolescent and adolescent rats: impact of age, sex, and drug dose

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