scholarly journals On the Digital Psychopharmacology of Valproic Acid in Mice

2020 ◽  
Author(s):  
John Samuel Bass ◽  
Anney Tuo ◽  
Linh Ton ◽  
Miranda J. Jankovic ◽  
Paarth K. Kapadia ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Open Field ◽  
Developmental Delays ◽  
Home Cage ◽  
Wheel Running ◽  
Drug Discontinuation ◽  
Fetal Exposure ◽  
Daily Ingestion ◽  
Field Assay ◽  
Technical Advances

AbstractObjectiveAntiepileptic drugs (AEDs) require daily ingestion for maximal seizure prophylaxis. Adverse psychiatric consequences of AEDs present as: (i) reversible changes in mood, anger, anxiety and/or irritability that often necessitate drug discontinuation, and (ii) autism and/or cognitive/psychomotor developmental delays following fetal exposure. Technical advances in quantifying naturalistic rodent behaviors may provide sensitive preclinical estimates of AED psychiatric tolerability and neuropsychiatric teratogenicity.MethodsUsing instrumented home-cage monitoring, we assessed how valproic acid (VPA, dissolved in sweetened drinking water) alters home-cage behavior in adult C57BL/6J mice and in the adult offspring of VPA-exposed breeder pairs. By utilizing a pup open field assay, we also examined how prenatal VPA exposure impacts early spontaneous exploratory behavior.ResultsAt 500-600mg/kg/d, chronic VPA produced hyperphagia and increased wheel-running without impacting sleep, activity and measures of risk aversion. When applied chronically to breeder pairs of mice, VPA prolonged the latency to viable litters without affecting litter size. Two-week old VPA-exposed pups displayed open field hypoactivity without alterations in thigmotaxis. As adults, prenatal VPA-exposed mice displayed active state fragmentation, hypophagia and increased wheel running, together with subtle alterations in home-cage dyadic behavior.InterpretationThrough automated home-cage assessments of C57BL/6J mice, we capture an ethologically centered psychopharmacological profile of enterally administered VPA that is aligned with human clinical experience. By characterizing the effects of pangestational VPA exposure, we discover novel murine expressions of pervasive neurodevelopment. Incorporating rigorous comprehensive assessments of neuropsychiatric tolerability may inform the design of future AEDs with improved neuropsychiatric safety profiles, both for patients and their offspring.

Chemically Contaminated Eel Fed to Pregnant and Lactating Mouse Dams Causes Hyperactivity in Their Offspring

2016 ◽  
Vol 86 (1-2) ◽  
pp. 36-47 ◽  
Author(s):  
Imen Dridi ◽  
Nidhal Soualeh ◽  
Torsten Bohn ◽  
Rachid Soulimani ◽  
Jaouad Bouayed
Keyword(s):  
Open Field ◽  
Early Life ◽  
Home Cage ◽  
Anguilla Anguilla ◽  
Acetylcholinesterase Activity ◽  
Female Offspring ◽  
Significant Inhibition ◽  
Standard Diet ◽  
Early Life Exposure ◽  
Cage Test

Abstract.This study examined whether perinatal exposure to polluted eels (Anguilla anguilla L.) induces changes in the locomotor activity of offspring mice across lifespan (post-natal days (PNDs) 47 – 329), using the open field and the home cage activity tests. Dams were exposed during gestation and lactation, through diets enriched in eels naturally contaminated with pollutants including PCBs. Analysis of the eel muscle focused on the six non-dioxin-like (NDL) indicator PCBs (Σ6 NDL-PCBs: 28, 52, 101, 138, 153 and 180). Four groups of dams (n = 10 per group) received either a standard diet without eels or eels (0.8 mg/kg/day) containing 85, 216, or 400 ng/kg/day of ϵ6 NDL-PCBs. The open field test showed that early-life exposure to polluted eels increased locomotion in female offspring of exposed dams but not in males, compared to controls. This hyperlocomotion appeared later in life, at PNDs 195 and 329 (up to 32 % increase, p < 0.05). In addition, overactivity was observed in the home cage test at PND 305: exposed offspring females showed a faster overall locomotion speed (3.6 – 4.2 cm/s) than controls (2.9 cm/s, p <0.05); again, males remained unaffected. Covered distances in the home cage test were only elevated significantly in offspring females exposed to highest PCB concentrations (3411 ± 590 cm vs. 1377 ± 114 cm, p < 0.001). These results suggest that early-life exposure to polluted eels containing dietary contaminants including PCBs caused late, persistent and gender-dependent neurobehavioral hyperactive effects in offspring mice. Furthermore, female hyperactivity was associated with a significant inhibition of acetylcholinesterase activity in the hippocampus and the prefrontal cortex.

Effects of prenatal ethanol exposure and early experience on home-cage and open-field activity in mice

1996 ◽  
Vol 18 (1) ◽  
pp. 59-65 ◽  
Author(s):  
Henning K. Mothes ◽  
Bernhard Opitz ◽  
Rolf Werner ◽  
Peter Clausing
Keyword(s):  
Open Field ◽  
Home Cage ◽  
Early Experience ◽  
Ethanol Exposure ◽  
Prenatal Ethanol Exposure ◽  
Open Field Activity ◽  
Field Activity

Preoptic implants of estradiol increase wheel running but not the open field activity of female rats

1985 ◽  
Vol 35 (6) ◽  
pp. 985-992 ◽  
Author(s):  
S FAHRBACH ◽  
R MEISEL ◽  
D PFAFF
Keyword(s):  
Open Field ◽  
Wheel Running ◽  
Female Rats ◽  
Open Field Activity ◽  
Field Activity

502 OPEN-FIELD BEHAVIOR AND GABA RECEPTOR DENSITY AFTER SPONTANEOUS WHEEL RUNNING AND TREADMILL TRAINING

1993 ◽  
Vol 25 (Supplement) ◽  
pp. S90 ◽  
Author(s):  
S. D. Youngstedt ◽  
R. K. Dishman FACSM ◽  
A. L. Dunn ◽  
M. A. Wilson ◽  
S. P. Wilson
Keyword(s):  
Open Field ◽  
Gaba Receptor ◽  
Wheel Running ◽  
Treadmill Training ◽  
Receptor Density ◽  
Open Field Behavior ◽  
Field Behavior

scholarly journals Home cage wheel running is an objective and clinically relevant method to assess inflammatory pain in male and female rats

2016 ◽  
Vol 263 ◽  
pp. 115-122 ◽  
Author(s):  
Ram Kandasamy ◽  
Jonas J. Calsbeek ◽  
Michael M. Morgan
Keyword(s):  
Inflammatory Pain ◽  
Home Cage ◽  
Wheel Running ◽  
Female Rats ◽  
Male And Female ◽  
Male And Female Rats

Increased open field locomotion and decreased striatal GABAA binding after activity wheel running

1996 ◽  
Vol 60 (3) ◽  
pp. 699-705 ◽  
Author(s):  
Rod K. Dishman ◽  
Andrea L. Dunn ◽  
Shawn D. Youngstedt ◽  
J.Mark Davis ◽  
Maria L. Burgess ◽  
...  
Keyword(s):  
Open Field ◽  
Wheel Running ◽  
Activity Wheel

Screening Approaches to Neurotoxicity: A Functional Observational Battery

1989 ◽  
Vol 8 (1) ◽  
pp. 85-93 ◽  
Author(s):  
Virginia Clayton Moser
Keyword(s):  
Open Field ◽  
Home Cage ◽  
Profile Analysis ◽  
Research Effort ◽  
Field Observations ◽  
Laboratory Rats ◽  
Primary Screening ◽  
Specificity And Sensitivity ◽  
Screening Approaches ◽  
Functional Observational Battery

Observational tests to assess the behavioral and neurologic integrity of laboratory rats have been advanced for use in the primary screening of chemicals to detect neurotoxic potential. To examine the use of such an approach, we are systematically using a functional observational battery (FOB) to characterize known neurotoxicants and to assess its selectivity, reliability, specificity, and sensitivity. Our FOB is a series of tests that includes home cage and open field observations, neuromuscular and sensorimotor tests, and physiologic measures. Described in this article are the compounds we have tested to date and how the data have been integrated to produce a profile of effects for each. We have found the FOB to be sensitive to a variety of neurotoxicants, whose effects can be distinguished using a type of profile analysis as illustrated herein. This research effort provides important information about both the execution and the interpretation of FOB studies.

scholarly journals Who's the Boss? Assessing Convergent Validity of Aggression Based Dominance Measures in Male Laboratory Mice, Mus Musculus

2021 ◽  
Vol 8 ◽  
Author(s):  
Amanda J. Barabas ◽  
Jeffrey R. Lucas ◽  
Marisa A. Erasmus ◽  
Heng-Wei Cheng ◽  
Brianna N. Gaskill
Keyword(s):  
Open Field ◽  
Test Scores ◽  
Convergent Validity ◽  
Discriminant Validity ◽  
Home Cage ◽  
Dominance Rank ◽  
Mitigation Strategies ◽  
Male Mice ◽  
Social Investigation ◽  
Tube Test

Aggression among group housed male mice continues to challenge laboratory animal researchers because mitigation strategies are generally applied at the cage level without a good understanding of how it affects the dominance hierarchy. Aggression within a group is typically displayed by the dominant mouse targeting lower ranking subordinates; thus, the strategies for preventing aggression may be more successful if applied specifically to the dominant mouse. Unfortunately, dominance rank is often not assessed because of time intensive observations or tests. Several correlates of dominance status have been identified, but none have been directly compared to home cage behavior in standard housing. This study assessed the convergent validity of three dominance correlates (urinary darcin, tube test score, preputial gland to body length ratio) with wound severity and rankings based on home cage behavior, using factor analysis. Discriminant validity with open field measures was assessed to determine if tube test scores are independent of anxiety. Cages were equally split between SJL and albino C57BL/6 strains and group sizes of 3 or 5 (N = 24). Home cage behavior was observed during the first week, and dominance measures were recorded over the second. After controlling for strain and group size, darcin and preputial ratio had strong loadings on the same factor, which was a significant predictor of home cage ranking showing strong convergent validity. Tube test scores were not significantly impacted by open field data, showing discriminant validity. Social network analysis revealed that despotic power structures were prevalent, aggressors were typically more active and rested away from cage mates, and the amount of social investigation and aggression performed by an individual were highly correlated. Data from this study show that darcin and preputial ratio are representative of home cage aggression and provide further insight into individual behavior patterns in group housed male mice.

scholarly journals An Inhibitory Medial Preoptic Circuit Mediates Innate Exploration

2021 ◽  
Vol 15 ◽  
Author(s):  
Jia Ryoo ◽  
Seahyung Park ◽  
Daesoo Kim
Keyword(s):  
Open Field ◽  
Preoptic Area ◽  
Normal Activity ◽  
Place Preference ◽  
Neural Pathways ◽  
Transporter Gene ◽  
Axonal Projections ◽  
Electrophysiological Recordings ◽  
Field Assay ◽  
Positive Valence

Animals have an innate motivation to explore objects and environments with unknown values. To this end, they need to activate neural pathways that enable exploration. Here, we reveal that photostimulation of a subset of medial preoptic area (MPA) neurons expressing the vesicular-GABA transporter gene (vgat+) and sending axonal projections to the ventrolateral periaqueductal gray (vPAG) increases exploration in a chamber but causes no place preference when tested there without photostimulation. Photoinhibition of MPAvgat–vPAG projections leads to no emotional changes as measured by normal activity in an open field assay. Electrophysiological recordings revealed that most GABAergic vPAG neurons are inhibited by MPAvgat neurons. In contrast to a previous report that suggested that MPAvgat–vPAG neurons may impart positive valence to induce place preference, our results suggest that these neurons can increase innate exploration.

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