Long-lasting effects of repeated ketamine administration in adult and adolescent rats

Bates, M.L. Shawn; Trujillo, Keith A.

doi:10.1016/j.bbr.2019.111928

Cited by 39 publications

(27 citation statements)

References 107 publications

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“…These results showed immediate effects of chronic unpredictable stress paradigm (CUS) in the group of experimental animals as increased locomotor activity and as a result of anticipating pain and stress, which is in consistency with previously conducted investigations. [11,12,13] The experimental group rats showed less spontaneous motoric activity than before ketamine application, which shows longer term effects of ketamine administration and its anxiolytic effects as well, which was also shown in study conducted by Bates and Trujillo, who also showed that repeated ketamine application might lead to addiction and with no statistical significance of cognitive deficits, memory and spatial learning, which is in consistency with our findings related to speed in swimming of animals and short memory where we also had no statistical significance [14]. The inability of low ketamine dose to affect memory can be due to the short half-life of ketamine.…”

Section: Discussionsupporting

confidence: 92%

Impact of ketamine on spontaneous coordinate activity and short memory behavior in rodents´ chronic unpredictable stress model

et al. 2021

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Introduction/Objective. This research aims to evaluate the impact of chronic stress on behavioral effects of ketamine, which are not sufficiently clear, still. Methods. Wistar male rats aged five weeks were used in the experiment. The animals were divided into two equal groups: control and experimental. After being exposed to a chronic unpredictable stress paradigm for 42 days, experimental rats had received a single injection of ketamine (10 mg/kg; day 45) as well as control group. The impact of ketamine was assessed using behavioral tests, spontaneous coordinate activity, and water maze tests for the evaluation of short-term memory. Results. The experimental group rats showed less spontaneous motoric activity than before ketamine application. Statistical significance was shown in gaining weight after time of ketamine application in control group and also in experimental group where they showed weight loss during stress paradigm and then increased their weight after ketamine application. There was no statistical significance in speed measurements in both groups showing no effects on short memory behavior. Conclusion. These findings show that ketamine in single subanesthetic dose has antidepressant and anxiolytic like effects in male rats exposed to chronic unpredictable stress paradigm

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Section: Discussionsupporting

confidence: 92%

Impact of ketamine on spontaneous coordinate activity and short memory behavior in rodents´ chronic unpredictable stress model

et al. 2021

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“…This finding is at odds with another investigation in our laboratory, where ketamine exposure later in adolescence/early adulthood had an adverse impact on the performance of drug-free rats subsequently tested in adulthood [38]. Conversely, the present results are consistent with those of Bates and Trujillo [63] who reported finding no cognitive deficits per se-although evidence of a mild spatial learning deficit-following adolescent exposure. In the present study, the drug washout period was considerably longer than the 20-day abstinence period used by Bates and Trujillo.…”

Section: Discussioncontrasting

confidence: 66%

“…Given the present results as well as others described earlier, our knowledge of the potential for ketamine to produce persisting alterations in behavior and cognition following adolescent exposure remains incomplete. Indeed, the effects of ketamine are complex, with interactions among multiple neurotransmitter systems [63], including those cholinergic, aminergic, and opioid-ergic in nature [74]. Further, a variety of non-NMDA mediated effects on glutamate receptors have been reported [75] [76].…”

Section: Discussionmentioning

confidence: 99%

Absence of Ketamine Effects on Learning & Memory Following Exposure during Early Adolescence: A Preliminary Report

O’Brien¹,

Compton²,

Davis³

et al. 2021

JBBS

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Traditionally, ketamine was considered useful as a dissociative anesthetic. More recently, ketamine has been examined for its effects as a fast-acting antidepressant, for treatment-resistant depression, and as a non-opiate treatment of chronic pain. Unfortunately, ketamine has enjoyed popularity as a recreational drug among both adolescents and young adults. While some research suggests the use of this drug during neurodevelopment is not without consequence, relatively little work has been conducted to examine the chronic effects of ketamine on the adolescent brain at different stages of neural development. Using a rodent model of development, we probed the effects of early adolescent exposure to ketamine. Between postnatal days 22 to 40, a period comprising early to mid-adolescence, rats were exposed to one of two doses of ketamine or saline. Beginning at 90 days of age and drug free for 50 days, a series of neuropsychological assessments were employed to examine general activity, spatial navigation, as well as nonspatial response learning. Contrary to prediction, except for differences in general activity levels, no spatial or nonspatial impairments were found among the drug-and saline-treated animals. The present results are considered in light of ketamine-associated effects found in a related study with older adolescent rats and the role of drug exposure during different points in adolescent brain development.

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“…The repeated administration of ketamine has served as an attractive model for conditions that are characterized by dissociative symptoms and cognitive impairment that are due to NMDAR hypofunction (e.g., schizophrenia [ 18 , 50 , 71 ]), often assayed preclinically as a deficit in NOR performance [ 72 ]. Interestingly, the acute hyperlocomotor response to ketamine that is triggered by NMDAR inhibition is more pronounced in preweanlings [ 73 ] and adolescents [ 74 , 75 ] relative to adults, and in females relative to males, especially during adolescence [ 76 , 77 ]. One interpretation of these observations is that younger rodents and females have an enhanced sensitivity to the NMDAR-inhibition-dependent actions of ketamine.…”

Section: Discussionmentioning

confidence: 99%

(R,S)-ketamine and (2R,6R)-hydroxynorketamine differentially affect memory as a function of dosing frequency

Riggs

Pereira

et al. 2021

Transl Psychiatry

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A single subanesthetic infusion of ketamine can rapidly alleviate symptoms of treatment-resistant major depression. Since repeated administration is required to sustain symptom remission, it is important to characterize the potential untoward effects of prolonged ketamine exposure. While studies suggest that ketamine can alter cognitive function, it is unclear to what extent these effects are modulated by the frequency or chronicity of treatment. To test this, male and female adolescent (postnatal day [PD] 35) and adult (PD 60) BALB/c mice were treated for four consecutive weeks, either daily or thrice-weekly, with (R,S)-ketamine (30 mg/kg, intraperitoneal) or its biologically active metabolite, (2R,6R)-hydroxynorketamine (HNK; 30 mg/kg, intraperitoneal). Following drug cessation, memory performance was assessed in three operationally distinct tasks: (1) novel object recognition to assess explicit memory, (2) Y-maze to assess working memory, and (3) passive avoidance to assess implicit memory. While drug exposure did not influence working memory performance, thrice-weekly ketamine and daily (2R,6R)-HNK led to explicit memory impairment in novel object recognition independent of sex or age of exposure. Daily (2R,6R)-HNK impaired implicit memory in the passive-avoidance task whereas thrice-weekly (2R,6R)-HNK tended to improve it. These differential effects on explicit and implicit memory possibly reflect the unique mechanisms by which ketamine and (2R,6R)-HNK alter the functional integrity of neural circuits that subserve these distinct cognitive domains, a topic of clinical and mechanistic relevance to their antidepressant actions. Our findings also provide additional support for the importance of dosing frequency in establishing the cognitive effects of repeated ketamine exposure.

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Long-lasting effects of repeated ketamine administration in adult and adolescent rats

Cited by 39 publications

References 107 publications

Impact of ketamine on spontaneous coordinate activity and short memory behavior in rodents´ chronic unpredictable stress model

Impact of ketamine on spontaneous coordinate activity and short memory behavior in rodents´ chronic unpredictable stress model

Absence of Ketamine Effects on Learning & Memory Following Exposure during Early Adolescence: A Preliminary Report

(R,S)-ketamine and (2R,6R)-hydroxynorketamine differentially affect memory as a function of dosing frequency

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Long-lasting effects of repeated ketamine administration in adult and adolescent rats

Cited by 39 publications

References 107 publications

Impact of ketamine on spontaneous coordinate activity and short memory behavior in rodents´ chronic unpredictable stress model

Impact of ketamine on spontaneous coordinate activity and short memory behavior in rodents´ chronic unpredictable stress model

Absence of Ketamine Effects on Learning &amp; Memory Following Exposure during Early Adolescence: A Preliminary Report

(R,S)-ketamine and (2R,6R)-hydroxynorketamine differentially affect memory as a function of dosing frequency

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Absence of Ketamine Effects on Learning & Memory Following Exposure during Early Adolescence: A Preliminary Report