Beijamini, V. | bioRxiv Science

bioRxiv2019

Ketamine effects on anxiety and fear-related behaviors: current literature evidence and new findings

Ketamine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, presents rapid and sustained antidepressant effect in clinical and preclinical studies. Regarding ketamine effects on anxiety, there is a widespread discordance among pre-clinical studies. To address this issue, the present study reviewed the literature (electronic database MEDLINE) to summarize the profile of ketamine effects in animal tests of anxiety/fear. We found that ketamine anxiety/fear-related effects may depend on the anxiety paradigm, schedule of ketamine administration and tested species. Moreover, there was no report of ketamine effects in animal tests of fear related to panic disorder (PD). Based on that finding, we evaluated if treatment with ketamine and another NMDA antagonist, MK-801, would induce acute and sustained (24 hours later) anxiolytic and/or panicolytic-like effects in animals exposed to the elevated T-maze (ETM). The ETM evaluates, in the same animal, conflict-evoked and fear behaviors, which are related, respectively, to generalized anxiety disorder and PD. Male Wistar rats were systemically treated with racemic ketamine (10, 30 and 80 mg/kg) or MK-801 (0.05 and 0.1 mg/kg) and tested in the ETM in the same day or 24 hours after their administration. Ketamine did not affect the behavioral tasks performed in the ETM acutely or 24 h later. MK-801 impaired inhibitory avoidance in the ETM only at 45 min post-injection, suggesting a rapid but not sustained anxiolytic-like effect. Altogether our results suggest that ketamine might have mixed effects in anxiety tests while it does not affect panic-related behaviors.\n\nHighlightsO_LIKetamine induces mixed effects in animal anxiety tests\nC_LIO_LIFew studies investigated the individual effects of S-ketamine in anxiety/fear tests\nC_LIO_LINone study evaluated the effects of R-Ketamine on anxiety/fear-related behaviors\nC_LIO_LISystemic ketamine does not affect panic-like behaviors in the elevated T-maze\nC_LI

animal behavior and cognition↗

bioRxiv2018

Refinement of anesthetic choice in procedures preceding psychopharmacological studies

RationalePrevious studies indicated that some general anesthetics induce long-term antidepressant and/or anxiolytic-like effects. This raises the concern about the use of anesthesia in surgeries that precede psycopharmacological tests, since it may be a potential bias on results depending on the experimental design used.\n\nObjectivesTo evaluate whether commonly used general anesthetics in surgeries preceding psychopharmacological tests would affect rat behavior in tests predictive of antidepressant or anxiolytic-like effects. We also evaluated whether prior anesthesia would interfere in the detection of the antidepressant-like effect of imipramine or the anxiolytic-like effect of diazepam.\n\nMethodsWe tested if a single exposure to subanesthetic or anesthetic doses of 2,2,2-tribromoethanol, chloral hydrate, thiopental or isoflurane would change rats behavior in the forced swimming test (FST) or in the elevated plus-maze (EPM) test, at 2 hours or 7 days after administration.\n\nResultsPrevious anesthesia with the aforementioned anesthetics did not change rat behavior in FST per se nor it changed the antidepressant-like effect induced by imipramine treatment. Rats previously anesthetized with tribromoethanol or chloral hydrate exhibited, respectively, anxiogenic-like or anxiolytic-like behavior in the EPM. Prior anesthesia with thiopental or isoflurane did not produce any per se effect in rat behavior in the EPM nor disturbed the anxiolytic-like effect of diazepam.\n\nConclusionOur results suggest that, in our experimental conditions, tribromoethanol and chloral hydrate are improper anesthetics for surgeries that precede behavioral tests related to anxiety. Isoflurane or thiopental may be suitable for anesthesia before evaluation in animal models predictive of antidepressant or anxiolytic-like effect.

neuroscience↗