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Binding Affinity, Selectivity, and Pharmacokinetics of the Oxytocin Receptor Antagonist L-368,899 in the Coyote (Canis latrans)

PhD,

BS,

PhD,

PhD, and

MS, DVM, PhD

L-368,899 is a selective small-molecule oxytocin receptor (OXTR) antagonist originally developed in the 1990s to prevent preterm labor. Although its utility for that purpose was limited, L-368,899 is now one of the most commonly used drugs in animal research for the selective blockade of neural OXTR after peripheral delivery. A growing number of rodent and primate studies have used L-368,899 to evaluate whether certain behaviors are oxytocin dependent. These studies have improved our understanding of oxytocin’s function in the brains of rodents and monkeys, but very little work has been done in other mammals, and only a single paper in macaques has provided any evidence that L-368,899 can be detected in the CNS after peripheral delivery. The current study sought to extend those findings in a novel species: coyotes (Canis latrans). Coyotes are ubiquitous North American canids that form long-term monogamous pair-bonds. Although monogamy is rare in rodents and primates, all wild canid species studied to date exhibit social monogamy. Coyotes are therefore an excellent model organism for the study of oxytocin and social bonds. Our goal was to determine whether L-368,899 is a viable candidate for future use in behavioral studies in coyotes. We used captive coyotes at the USDA National Wildlife Research Center’s Predator Research Facility to evaluate the pharmacokinetics of L-368,899 in blood and CSF during a 90-min time course after intramuscular injection. We then characterized the binding affinity and selectivity of L-368,899 to coyote OXTR and the structurally similar vasopressin 1a receptor. We found that L-368,899 peaked in CSF at 15 to 30 min after intramuscular injection and slowly accumulated in blood. L-368,899 was 40 times more selective for OXTR than vasopressin 1a receptors and bound to the coyote OXTR with an affinity of 12 nM. These features of L-368,899 support its utility in future studies to probe the oxytocin system of coyotes.

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Consistency in Reporting of Loss of Righting Reflex for Assessment of General Anesthesia in Rats and Mice: A Systematic Review

BSc,

BA, MLIS, and

BVSc, PhD

DOI: 10.30802/AALAS-CM-23-000063

General anesthesia induces a reversible loss of consciousness (LOC), a state that is characterized by the inability to feel pain. Identifying LOC in animals poses unique challenges, because the method most commonly used in humans, responding to questions, cannot be used in animals. For over a century, loss of righting reflex (LORR) has been used to assess LOC in animals. This is the only animal method that correlates directly with LOC in humans and has become the standard proxy measure used in research. However, the reporting of how LORR is assessed varies extensively. This systematic literature review examined the consistency and completeness of LORR methods used in rats and mice. The terms ‘righting reflex,’ ‘anesthesia,’ ‘conscious,’ ‘rats,’ ‘mice,’ and their derivatives were used to search 5 electronic databases. The abstracts of the 985 articles identified were screened for indications that the study assessed LORR in mice or rats. Full texts of selected articles were reviewed for LORR methodological completeness, with reported methods categorized by 1) animal placement method, 2) behavioral presence of righting reflex, 3) duration of LORR testing, 4) behavioral LORR, and 5) animal position for testing LORR. Only 22 papers reported on all 5 methodological categories. Of the 22 papers, 21 used unique LORR methodologies, with descriptions of LORR methods differing in at least one category as compared with all other studies. This variability indicates that even papers that included all 5 categories still had substantial differences in their methodological descriptions. These findings reveal substantial inconsistencies in LORR methodology and reporting in the biomedical literature likely compromising study replicability and data interpretation.

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in-text ref citation test High-pressure Hydrodynamic Injection as a Method of Establishing Hepatitis B Virus Infection in Mice

, and

DOI: 10.30802/AALAS-CM-23-000050.test1

Abstract

Among several existing mouse models for hepatitis B virus (HBV) infection, the high-pressure hydrodynamic injection (HDI) method is frequently used in HBV research due to its economic advantages and ease of implementation. The use of the HDI method is influenced by factors such as mouse genetic background, age, sex, and the type of HBV plasmid used. This overview provides a multidimensional analysis and comparison of various factors that influence the effectiveness of the HBV mouse model established through HDI. The goal is to provide a summary of information for researchers who create HBV models in mice.

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High-pressure Hydrodynamic Injection as a Method of Establishing Hepatitis B Virus Infection in Mice

, and

DOI: 10.30802/AALAS-CM-23-000050

Abstract

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Erratum: AC-DC Electropenetrography as a Tool to Quantify Probing and Ingestion Behaviors of the Yellow Fever Mosquito (Aedes aegypti) on Mice in Biocontainment

DOI: 10.30802/AALAS-CM-24-000009

This corrects the article DOI:

10.30802/AALAS-CM-23-000037

When the above article was first published in the Vol 73 No 6 (December 2023) issue of Comparative Medicine, figure images were incorrectly associated with the figure legends. The correct version of this article has been reprinted in full in volume 74, issue 1 of the February issue of Comparative Medicine.

The publisher apologizes for this error and any inconvenience caused.

DOI: 10.30802/AALAS-CM-24-000009

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Erratum: Pharmacokinetics of a Single Transdermal Dose of Mirtazapine in Rhesus Macaques (Macaca mulatta)

DOI: 10.30802/AALAS-CM-24-000010

This corrects the article DOI:

10.30802/AALAS-CM-23-000060

In the original article entitled “Pharmacokinetics of a Single Transdermal Dose of Mirtazapine in Rhesus Macaques (Macaca mulatta),” published in Vol 73, Issue 6 (December 2023), the figure images were incorrectly duplicated and called out incorrectly in the text. The correct version of this article has been reprinted in full in Vol 74, Issue 1 (February 2024) of Comparative Medicine.

The publisher apologizes for this error and any inconvenience caused.

DOI: 10.30802/AALAS-CM-24-000010

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Erratum: Unique Presentations of Burkholderia gladioli Infections in Several Strains of Immunocompromised Mice

DOI: 10.30802/AALAS-CM-24-000012

This corrects the article DOI:

10.30802/AALAS-CM-23-000016

In the original article entitled “Unique Presentations of Burkholderia gladioli Infections in Several Strains of Immunocompromised Mice,” published in Vol 73, Issue 5 (October 2023), pages 391 to 397, there is an accidental error in the first sentence of the Introduction section, which states that Burkholderia gladioli is nonmotile when in fact B. gladioli is considered to be motile. Burkholderia gladioli is correctly described as motile in the Discussion.

DOI: 10.30802/AALAS-CM-24-000012

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Binding Affinity, Selectivity, and Pharmacokinetics of the Oxytocin Receptor Antagonist L-368,899 in the Coyote (Canis latrans)

Consistency in Reporting of Loss of Righting Reflex for Assessment of General Anesthesia in Rats and Mice: A Systematic Review

in-text ref citation test High-pressure Hydrodynamic Injection as a Method of Establishing Hepatitis B Virus Infection in Mice

Abstract

High-pressure Hydrodynamic Injection as a Method of Establishing Hepatitis B Virus Infection in Mice

Abstract

Erratum: AC-DC Electropenetrography as a Tool to Quantify Probing and Ingestion Behaviors of the Yellow Fever Mosquito (Aedes aegypti) on Mice in Biocontainment

Erratum: Pharmacokinetics of a Single Transdermal Dose of Mirtazapine in Rhesus Macaques (Macaca mulatta)

Erratum: Unique Presentations of Burkholderia gladioli Infections in Several Strains of Immunocompromised Mice

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