-
Comparative Medicine Oct 2019Female urine-induced male mice ultrasonic vocalizations (FiUSV) are ultrasonic vocalizations produced by adult male mice after presentation of adult female urine,...
Female urine-induced male mice ultrasonic vocalizations (FiUSV) are ultrasonic vocalizations produced by adult male mice after presentation of adult female urine, whereas intruder-induced ultrasonic vocalizations (IiUSV) are produced by resident adult female mice when interacting with an intruder female mouse. These affiliative behaviors may be reduced when mice have decreased wellbeing or are in pain and distress. To determine whether FiUSV and IiUSV can be used as proxy indicators of animal wellbeing, we assessed FiUSV produced by male C57BL/6J mice in response to female urine and IiUSV produced by female C57BL/6J mice in response to a female intruder at baseline and 1 and 3 h after administration of a sublethal dose of LPS (6 or 12.5 mg/kg IP) or an equal volume of saline. Behavior was assessed by evaluating orbital tightness, posture, and piloerection immediately after USV collection. We hypothesized that LPS-injected mice would have a decreased inclination to mate or to interact with same-sex conspecifics and therefore would produce fewer USV. At baseline, 32 of 33 male mice produced FiUSV (149 ± 127 USV in 2 min), whereas all 36 female mice produced IiUSV (370 ± 156 USV in 2 min). Saline-injected mice showed no change from baseline at the 1- and 3-h time points, whereas LPS-injected mice demonstrated significantly fewer USV than baseline, producing no USV at both 1 and 3 h. According to orbital tightness, posture, and piloerection, LPS-injected mice showed signs of poor wellbeing at 3 h but not 1 h. These findings indicate that FiUSV and IiUSV can be used as proxy indicators of animal wellbeing associated with acute inflammation in mice and can be detected before the onset of clinical signs.
Topics: Animals; Female; Male; Mice; Mice, Inbred C57BL; Vocalization, Animal
PubMed: 31578163
DOI: 10.30802/AALAS-CM-18-000147 -
Frontiers in Neurology 2019The human skin is a highly specialized organ for receiving sensory information but also to preserve the body's homeostasis. These functions are mediated by cutaneous... (Review)
Review
The human skin is a highly specialized organ for receiving sensory information but also to preserve the body's homeostasis. These functions are mediated by cutaneous small nerve fibers which display a complex anatomical architecture and are commonly classified into cutaneous A-beta, A-delta and C-fibers based on their diameter, myelinization, and velocity of conduction of action potentials. Knowledge on structure and function of these nerve fibers is relevant as they are selectively targeted by various autonomic neuropathies such as diabetic neuropathy or Parkinson's disease. Functional integrity of autonomic skin nerve fibers can be assessed by quantitative analysis of cutaneous responses to local pharmacological induction of axon reflex responses which result in dilation of cutaneous vessels, sweating, or piloerection depending on the agent used to stimulate this neurogenic response. Sensory fibers can be assessed using quantitative sensory test. Complementing these functional assessments, immunohistochemical staining of superficial skin biopsies allow analysis of structural integrity of cutaneous nerve fibers, a technique which has gained attention due to its capacity of detecting pathogenic depositions of alpha-synuclein in patients with Parkinson's disease. Here, we reviewed the current literature on the anatomy and functional pathways of the cutaneous autonomic nervous system as well as diagnostic techniques to assess its functional and structural integrity.
PubMed: 31551921
DOI: 10.3389/fneur.2019.00970 -
Physiology & Behavior Nov 2019Measuring body surface temperature changes with infrared thermography has recently been put forward as a non-invasive alternative measure of physiological correlates of...
Measuring body surface temperature changes with infrared thermography has recently been put forward as a non-invasive alternative measure of physiological correlates of emotional reactions. In particular, the nasal region seems to be highly sensitive to emotional reactions. Several studies suggest that nasal temperature is negatively correlated with the level of arousal in humans and other primates, but some studies provide inconsistent results. Our goal was to establish the use of infrared thermography to quantify emotional reactions in common marmosets (Callithrix jacchus), with a focus on the nasal region. To do so we exposed 17 common marmosets to a set of positive, negative and control stimuli (positive: preferred food, playback of food calls; negative: playback of aggressive vocalizations, teasing; control: no stimulus). We compared nasal temperature before and after the stimuli and expected that highly aroused emotional states would lead to a drop in nasal temperature. To validate the thermography measure, we coded piloerection of the tail as an independent measure of arousal and expected a negative correlation between the two measures. Finally, we coded physical activity to exclude its potential confounding impact on nasal temperature. Our results show that all predictions were met: the animals showed a strong decrease in nasal temperature after the presentation of negative arousing stimuli (teasing, playback of aggressive vocalizations). Furthermore, these changes in nasal temperature were correlated with piloerection of the tail and could not be explained by changes in physical activity. In the positive and the control conditions, we found systematic sex differences: in males, the preferred food, the playbacks of food calls, as well as the control stimulus led to an increase in nasal temperature, whereas in females the temperature remained stable (preferred food, control) or decreased (playback of food calls). Based on naturalistic observations that document higher food motivation and competition among female marmosets, as well as stronger reactions to separation from group members in male marmosets, these sex differences corroborate a negative correlation between arousal and nasal temperature. Overall, our results support that measuring nasal temperature by infrared thermography is a promising method to quantify emotional arousal in common marmosets in a fully non-invasive and highly objective way.
Topics: Animals; Arousal; Body Temperature; Callithrix; Emotions; Female; Male; Sex Characteristics; Skin Physiological Phenomena; Thermography
PubMed: 31487492
DOI: 10.1016/j.physbeh.2019.112672 -
Neurocritical Care Oct 2019
Topics: Adolescent; Aggression; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Athetosis; Chorea; Diagnosis, Differential; Dyskinesias; Encephalitis; Exanthema; Fever; Glasgow Coma Scale; HIV Infections; HIV Seropositivity; Humans; Irritable Mood; Magnetic Resonance Imaging; Male; Muscle Hypertonia; Piloerection; Psychotic Disorders; Reflex, Abnormal; Seizures; Tachycardia
PubMed: 31410769
DOI: 10.1007/s12028-019-00805-5 -
Journal of Cosmetic Dermatology Dec 2019Approximately 40% of women experience excessive hair shedding when washing their hair. Previously, we have demonstrated that a topically applied α1 adrenergic receptor...
BACKGROUND
Approximately 40% of women experience excessive hair shedding when washing their hair. Previously, we have demonstrated that a topically applied α1 adrenergic receptor agonist can be used to contract the arrector pili muscle of the follicular unit (ie, produce "goose bumps"), increasing the force required to pluck hair by as much as 400%. Subsequently, we reported a topical cosmetic solution containing an α1 adrenergic receptor agonist that reduced hair shedding during brushing by a maximum of 77%.
AIMS
In this communication, we explore a novel mechanism to contract the arrector pili muscle. Trace amine-associated receptors (TAAR) have been shown to regulate smooth muscle tone in blood vessels, but have not been reported to be present in the skin. Here, we report on the anti-shedding efficacy of a shampoo containing a selective TAAR agonist, tyramine hydrochloride.
METHODS
A single-blinded crossover study was designed to test the efficacy of the novel shampoo versus placebo in reducing hairs lost during brushing.
RESULTS
In this study, the novel TAAR shampoo reduced hair shedding during brushing by 31% in a cohort of 24 women with a maximum reduction of 77%.
CONCLUSIONS
A shampoo formulated with a selective TAAR agonist was demonstrated to contract the arrector pili muscle and reduce hair shedding subsequent to washing.
Topics: Adolescent; Adult; Aged; Cross-Over Studies; Female; Hair Follicle; Hair Preparations; Humans; Middle Aged; Muscle Contraction; Muscle, Smooth; Receptors, G-Protein-Coupled; Tyramine; Young Adult
PubMed: 31264766
DOI: 10.1111/jocd.13054 -
Physiology & Behavior Sep 2019While investigating the effect of alternative energy substrates on extracellular brain glucose or lactate, Béland-Millar (2017) noted a reduction of physical activity...
The impact of lactic acid and medium chain triglyceride on blood glucose, lactate and diurnal motor activity: A re-examination of a treatment of major depression using lactic acid.
While investigating the effect of alternative energy substrates on extracellular brain glucose or lactate, Béland-Millar (2017) noted a reduction of physical activity after intraperitoneal administration of lactate and ketone bodies. These observations were similar to an older study that examined the impact of drinking a sodium lactate/lactic acid solution before sleep in hospitalized patients with major depression. Patients and control participants self-reported drowsiness, early sleep onset and better overall sleep after consumption. Some patients showed improved mood after several days of treatment. We re-evaluated the effects of the solution used (0.59 g/kg) as well as several smaller doses (0.47, 0.35, 0.24 and 0.12 g/kg) on blood lactate and glucose in CD-1 mice and on sleep onset associated activity reduction. Because of adverse effects with the lactate/lactic acid solution, we also examined the effects of a medium chain triglyceride (MCT) solution (10, 5, 2.5, and 1 ml/kg) on blood lactate and glucose. Oral gavage administration of lactic acid/lactate produced adverse effects particularly for the largest doses. However consumption of 10 and 5 ml/kg volumes of MCT oils significantly increased blood lactate concentration to levels comparable to Lowenbach's solution without piloerection indicative of adverse effects. To evaluate pre-sleep activity reduction produced by lactate, mice were intraperitoneally administered diluted sodium lactate (2.0 g/kg, 1.0 g/kg, 0.5 g/kg, 0.25 g/kg, or saline) for 6 days, 120 min before their sleep period and their running activity was measured. Larger lactate doses reduced pre-sleep running each day up to 60 min post injection. Smaller doses reduced running after a single treatment only. These results suggest that the modulation of blood lactate levels may be useful in treating sleep onset problems associated with depression.
Topics: Animals; Blood Glucose; Circadian Rhythm; Depressive Disorder, Major; Dose-Response Relationship, Drug; Humans; Lactic Acid; Male; Mice; Motor Activity; Triglycerides
PubMed: 31175891
DOI: 10.1016/j.physbeh.2019.112569 -
PloS One 2019Recently the anti-viral effects of prophylactic treatment with the low-molecular-weight heparan sulfate mimetic PG545 in Ross River virus (RRV) infected mice were...
Recently the anti-viral effects of prophylactic treatment with the low-molecular-weight heparan sulfate mimetic PG545 in Ross River virus (RRV) infected mice were reported. We further investigated the related, transient pathophysiology of PG545 drug treatment in RRV-infected and mock-infected PG545-treated mice. PG545 treatment resulted in mild lethargy and piloerection, on days after the drug administration. Mice were treated with two or three doses of PG545 within a ten-day period and were subsequently culled at peak disease or at disease resolution. The treatment responses of the spleen and liver were assessed through histology, flow cytometry, gene arrays and serum biochemistry. Microscopy showed an expanded red pulp in the spleen following either two or three treatments with PG545. The red pulp expansion was further demonstrated by the proliferation of megakaryocytes and erythrocyte precursors within the spleen. In addition, flow cytometry and gene array analyses revealed a reduction of lymphocytes within the spleens of PG545-treated mice. Previously unreported, RRV-induced elevations of aspartate aminotransferase (AST) and alanine transaminase (ALT) enzymes and creatinine were also noted in the RRV-infected mice. However, PG545 only reduced AST and ALT levels but not the creatinine levels in infected mice during treatment. Mice treated with three doses of PG545 also showed hepatosplenomegaly and anaemia, which were reversed upon discontinuation of the treatment. In summary, this study demonstrates that dose and frequency related haemopoietic pathophysiology such as hepatosplenomegaly and anaemia, occurred in C57BL/6 mice treated with PG545. However, this effect was reversible once drug administration is terminated.
Topics: Alanine Transaminase; Alphavirus Infections; Animals; Aspartate Aminotransferases; Glucuronidase; Liver; Lymphocytes; Mice; Mice, Inbred C57BL; Ross River virus; Saponins; Spleen
PubMed: 31170255
DOI: 10.1371/journal.pone.0217998 -
PloS One 2019This study aimed to evaluate the potential adverse effects of the dermal administration of Dillenia indica Linnaeus (D. indica) fruit extract in healthy rodents; the...
This study aimed to evaluate the potential adverse effects of the dermal administration of Dillenia indica Linnaeus (D. indica) fruit extract in healthy rodents; the extract was standardized to betulinic acid. In the initial phase, the acute effects were evaluated on the skin application site of a single extract dose. A skin irritation test was performed in male Wistar rats (n = 8/group) receiving the extract (50-150 mg/mL) with betulinic acid (0.5-1.5%, respectively). A photosensitivity test was performed in male BALB/c mice (n = 6/group) receiving the extract (150 mg/mL). Afterwards, other BALB/c mice (n = 20, male:female, 1:1) were used to assess the systemic alterations caused by 14 daily repeated doses (150 mg/mL) by monitoring the effects on mortality, body morphology, behavior, nutrition status, neuromotor reactions, organ morphology and weight, and blood tests. At this time, 0.5 mg/mL clobetasol was used as the positive control. The skin irritation index suggested that negligible skin irritation had occurred, even when the extract was applied to the rat skin at 150 mg/mL. However, the extract acted as a photosensitizer on mouse skin, showing a photosensitizing activity close to that of 10 mg/mL 5-methoxypsoralen. Repeated doses caused no mouse mortality, aggressiveness, piloerection, diarrhea, convulsions, neuromotor alterations or nutrition status changes. The mouse organ weights did not change, and the mice did not have alterations in their blood compositions. Clobetasol caused a reduction in the mononuclear leukocyte numbers. In general, the data suggest that the extract was safe in healthy rodents but indicate that caution should be taken with the photosensitizing activity; in addition, this activity should be further explored as it may be useful for phototherapeutic drug development.
Topics: Administration, Cutaneous; Animals; Clobetasol; Dilleniaceae; Fruit; Humans; Leukocytes, Mononuclear; Mice; Pentacyclic Triterpenes; Photosensitizing Agents; Plant Extracts; Rats; Skin; Skin Irritancy Tests; Triterpenes; Betulinic Acid
PubMed: 31150479
DOI: 10.1371/journal.pone.0217718 -
Laboratory Animals Apr 2020In this study, the effect of four anaesthetic protocols that included the combination of xylazine (X) and ketamine (K) with acepromazine (A) and opioids (methadone (Me),...
In this study, the effect of four anaesthetic protocols that included the combination of xylazine (X) and ketamine (K) with acepromazine (A) and opioids (methadone (Me), morphine (Mo) or tramadol (T)) was evaluated in laboratory rats of both sexes. Ultrasonic vocalization (USV) was used as an indicator of pain during the recovery period. The objective was to evaluate the physiological parameters and the analgesic effect of each protocol to determine which protocol was the safest and fulfil the requirements of a balanced anaesthesia. The better protocols were the XKA protocol for both sexes and the XKMe protocol for females because the combinations achieve surgical plane of anaesthesia in rats. However, pain assessment during the formalin test revealed that rats anaesthetized with XKA produced more numbers of USV, suggesting that it is not a good protocol for the control of immediate postoperative pain. All protocols produced depression in body temperature and respiratory and heart rates, and had important effects, such as micturition and maintenance of open eyes. Only rats anaesthetized with XKA protocol did not present piloerection. These results demonstrated that good monitoring and care during anaesthesia must be included to prevent complications that compromise the life of the animal and to ensure a good recovery. The inclusion of analgesia in anaesthesia protocols must be used routinely, ensuring minimal presence of pain and thus more reliable results in the experimental procedures.
Topics: Acepromazine; Analgesics; Analgesics, Opioid; Animals; Drug Combinations; Female; Ketamine; Male; Rats; Ultrasonic Waves; Vocalization, Animal; Xylazine
PubMed: 31142228
DOI: 10.1177/0023677219850211 -
Journal of Pharmacological and... 2019Irwin/FOB testing is routinely conducted to investigate the neurofunctional integrity of laboratory animals during preclinical development of new drugs, however, the...
INTRODUCTION
Irwin/FOB testing is routinely conducted to investigate the neurofunctional integrity of laboratory animals during preclinical development of new drugs, however, the study design frequently varies to meet specific needs. Representatives of several European-based pharmaceutical companies performed a "state-of-the-art" assessment of how they conduct their CNS safety evaluation using Irwin/FOB tests.
METHODS
This assessment consisted of (1) a survey of current/historical practice, (2) an evaluation of historical studies with reference compounds (amphetamine, chlorpromazine) to determine intercompany reproducibility of results, and (3) an interlaboratory test using reference compounds (MK-801, chlorpromazine) to determine whether partially standardized conditions (animals, sex, doses, vehicles, administration route, observation time points, systemic exposure) might reduce variability of results.
RESULTS
Our survey revealed several similarities, e.g., main endpoints of home cage and openfield observations, species, and positive control substances, but also a high level of heterogeneity between different companies with regard to behavioral endpoints during handling and reflex testing, scoring, group size, and timing of studies. Analysis of heterogeneously designed historical studies with amphetamine and chlorpromazine showed the anticipated behavioral changes, albeit with quantitative variability, and identified more robust (e.g., activity, posture, muscle tone, startle reflex, body temperature) and less robust (piloerection, stereotypical behavior, palpebral closure, respiration) Irwin/FOB parameters. A partially standardized interlaboratory test with MK-801 and chlorpromazine showed the expected behavioral changes and principally confirmed the historically-based more/less robust Irwin/FOB parameters, however, it also showed exposure variability and did not show a markedly reduced quantitative variability of behavioral results.
DISCUSSION
Our survey and intercompany test results demonstrate certain heterogeneity in design and conduct of Irwin/FOB tests by pharmaceutical companies. Although the general behavioral profiles for the reference compounds were consistently found, quantitative variability of results remained even under partially standardized conditions. This suggests the importance of a high level of standardization with regard to the Irwin/FOB test modification used, scoring system, and observer training, in order to achieve an improved intercompany comparability of Irwin/FOB results.
PubMed: 30928509
DOI: 10.1016/j.vascn.2019.03.002