Naloxone increases ketamine-induced hyperactivity in the open field in female rats

Wilson, Christopher; Cone, K. V.; Kercher, Melanie; Hibbitts, J.T.; Fischer, Jessica; Lake, Amber Van; Sumner, Jean E.

doi:10.1016/j.pbb.2005.03.018

Cited by 17 publications

(11 citation statements)

References 20 publications

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“…Our data on a single injection of this drug also complement an emerging literature on rodent ketamine sex differences (or similarities, including investigations of females instead of just males) with respect to: chronic dosing of ketamine (Thelen et al, 2016), ketamine enantiomers (Chang et al, 2018), drug self-administration or addictive behaviors (Schoepfer et al, 2019;Wright et al, 2019;, hyperactivity (McDougall et al, 2019;Wilson et al, 2005Wilson et al, , 2007, neurohormonal regulation (Dossat et al, 2018;Picard et al, 2019;Saland et al, 2016;Wright et al, 2017), fear conditioning (Mastrodonato et al, 2018), and synaptic mechanisms (Sarkar & Kabbaj, 2016;Strong et al, 2017;. These previous studies, as well as our data here and the literature described earlier in the Discussion, highlight a variety of sex differences in response to ketamine in mice and rats, and collectively underscore the importance of gaining a greater understanding of the neural mechanisms that mediate these sex differences and how they may translate to human psychopathology.…”

Section: Discussionsupporting

confidence: 60%

Sex- and stress-dependent effects of a single injection of ketamine on open field and forced swim behavior

Fitzgerald

Kounelis-Wuillaume

Gheidi

et al. 2021

Stress

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Ketamine has emerged as a novel treatment for common psychiatric conditions such as Major Depressive Disorder (MDD) and anxiety disorders, many of which can be initiated and exacerbated by psychological stress. Sex differences in the frequency of both anxiety and depressive disorders are well known and could be due to sex differences in neuroendocrine responses to stress. Ketamine is known to modulate the hormonal response to stress, specifically corticosterone. It is not clear if the acute effect of ketamine on corticosterone differs by sex, or what role this could play in subsequent behavior.Here we test whether a single injection of (R,S)-ketamine (30 mg/kg, i.p.), administered either with or without unpredictable chronic stress (UCS), has different sustained effects on open field test (OFT), elevated zero maze (EZM) or forced swim test (FST) behavior in female versus male C57BL/6J mice. In the OFT (24 h post-injection), ketamine increased center square exploration in males but not females. In contrast, in the FST (72 h post-injection), females showed a trend toward a decrease in immobility after ketamine whereas males were not strongly modulated. These behavioral effects of ketamine were stronger in the presence of UCS than in unstressed animals. UCS animals also showed lower corticosterone after injection than unstressed animals, and in the presence of UCS ketamine increased corticosterone; these effects were similar in both sexes. Corticosterone post-injection did not predict subsequent behavior. These findings complement a growing preclinical literature suggesting both stress-dependency and sex differences in OFT and FST behavioral responses to ketamine.

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Section: Discussionsupporting

confidence: 60%

Sex- and stress-dependent effects of a single injection of ketamine on open field and forced swim behavior

Fitzgerald

Kounelis-Wuillaume

Gheidi

et al. 2021

Stress

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“…Meanwhile this same aberrant swimming pattern in zebrafish can be induced by another NMDA receptor blockade, MK801 [47]. These results are pretty similar with the locomotion of rodents induced by NMDA antagonists [48].…”

Section: Functional Damage Of Ketamine In Zebrafish's Nervous Systemsupporting

confidence: 69%

Zebrafish as a New Platform Used in Exploration of Ketamine-Induced Neurodevelopmental Toxicity

Ruan¹

2015

J Clin Exp Pathol

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We have modified the abstract as 'Previous studies have already found out that commonly used anesthetic, ketamine, has toxic effects on neurodevelopment. Unlike most rodent models just focusing on neuronal apoptosis caused by ketamine, early stages of neuron development abnormality in zebrafish can be assessed in vivo because of the transparent embryos and larve. And also thanks to its cost-efficiency and quick reproduction, large-scale behavior analyses and gene screens can be conducted in zebrafish. Besides, the whole genome of zebrafish has already been sequenced and its gene functions are highly conserved during evolution, which makes the experiments more reliable on zebrafish model. So Zebrafish has obvious advantages in the researches of ketamine neurotoxicity over the conventional animal models (such as mice). Within this paper we illuminate how we can use this model to study ketamine neurotoxicity. In the future, along with more advanced genetic technologies joining this platform will not only make up for conventional models to deeply understand neurodevelopmental toxicity of ketamine, but also might provide the unique insight to the field of neurodevelopment and neurotoxicity impaired by other drugs

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“…These rodent studies typically administer a single, systemic injection of ketamine, and then monitor behavior in the acute period afterward, or 24 h or more later ( 14 ). It is important to measure behavior beyond the acute time window, such as at the 24 h point, since ketamine has acute dissociative-like properties that can result in hyperlocomotion ( 21 , 22 ) and be confounded with immobility-related behavior in the FST. For these reasons, when studying any drug in the FST it is important to also measure locomotor activity in an assay such as the open field test, to gauge whether changes observed in the FST are confounded with generalized hyperactivity (or hypoactivity).…”

Section: Introductionmentioning

confidence: 99%

Repeated Dosing of Ketamine in the Forced Swim Test: Are Multiple Shots Better Than One?

2021

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The anesthetic drug ketamine has been successfully repurposed as an antidepressant in human subjects. This represents a breakthrough for clinical psychopharmacology, because unlike monoaminergic antidepressants, ketamine has rapid onset, including in Major Depressive Disorder (MDD) that is resistant to conventional pharmacotherapy. This rapid therapeutic onset suggests a unique mechanism of action, which continues to be investigated in reverse translational studies in rodents. A large fraction of rodent and human studies of ketamine have focused on the effects of only a single administration of ketamine, which presents a problem because MDD is typically a persistent illness that may require ongoing treatment with this drug to prevent relapse. Here we review behavioral studies in rodents that used repeated dosing of ketamine in the forced swim test (FST), with an eye toward eventual mechanistic studies. A subset of these studies carried out additional experiments with only a single injection of ketamine for comparison, and several studies used chronic psychosocial stress, where stress is a known causative factor in some cases of MDD. We find that repeated ketamine can in some cases paradoxically produce increases in immobility in the FST, especially at high doses such as 50 or 100 mg/kg. Several studies however provide evidence that repeated dosing is more effective than a single dose at decreasing immobility, including behavioral effects that last longer. Collectively, this growing literature suggests that repeated dosing of ketamine has prominent depression-related effects in rodents, and further investigation may help optimize the use of this drug in humans experiencing MDD.

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Naloxone increases ketamine-induced hyperactivity in the open field in female rats

Cited by 17 publications

References 20 publications

Sex- and stress-dependent effects of a single injection of ketamine on open field and forced swim behavior

Sex- and stress-dependent effects of a single injection of ketamine on open field and forced swim behavior

Zebrafish as a New Platform Used in Exploration of Ketamine-Induced Neurodevelopmental Toxicity

Repeated Dosing of Ketamine in the Forced Swim Test: Are Multiple Shots Better Than One?

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