Assessment of serotonin in serum,plasma, and platelets of aggressive dogs

Canine aggression is the most common reason for the referral of dogs to behavior practices. In addition, dog bites represent an important problem for public health and animal welfare. The serotonergic system is believed to play an important role in modulating aggression. The aim of the present study was (1) to assess the suitability of different types of blood samples for measuring circulating serotonin in canine clinical studies, and (2) to investigate the relationship between the serotonergic system and canine aggression. The assessment of serotonin was simultaneously carried out in serum, plasma, and platelets of 28 aggressive and 10 nonaggressive dogs with an enzyme immunoassay technique. The mean serotonin concentration in aggressive dogs was significantly lower than in nonaggressive dogs in all the assayed samples. These findings suggest an inverse relationship between the activity of the serotonergic system and canine aggression. Considering the simplicity of the methodology, the authors propose sampling serum as the most suitable method for measuring circulating serotonin in dogs.     

Neuro-imaging the serotonin 2A receptor as a valid biomarker for canine behavioural disorders

The serotonergic system is disturbed in different mood and affective disorders, with especially the serotonin (5-HT) 2A receptor involved in impulsive aggressiveness and anxiety. The aim of the study was to evaluate the involvement of the brain 5-HT 2A receptor in dogs with different behavioural disorders. Three groups of drug naive dogs were studied: 22 dogs showing impulsive aggressive behaviour, 22 showing normal behaviour, and 22 showing anxious behaviour. The serotonin 2A receptor was evaluated with Single Photon Emission Computed Tomography (SPECT) and the serotonin 2A receptor-selective radiopharmaceutical (123)I-R91150. A serotonin 2A receptor binding index (BI), proportional to the cortical receptor density, was calculated. A receiver operating characteristic (ROC) analysis was performed to determine cut-off values at which optimal sensitivity and specificity are achieved and to evaluate the general performance of the BI in reflecting the state of the dog, i.e., impulsive aggressive, normal or anxious. Significantly (P<0.0056) altered 5-HT 2A receptor binding indices were found in bilateral frontal, temporal and occipital cortical brain areas of the dogs behaving abnormally, with consistently increased BI in impulsive aggressive dogs and decreased BI in anxious dogs. These results provide clear evidence for a disturbed serotonergic balance in canine impulsive aggression and anxiety disorders. A right frontal cut-off value of ≥1.92 with 86.4% sensitivity and 2.3% (1-specificity) was obtained for the impulsive aggressive dogs. Differentiating the anxious dogs from the rest of the population was possible with a cut-off value of ≤1.73 with 86.4% sensitivity and 18.2% (1-specificity). We conclude that SPECT imaging with the radioligand (123)I-R91150 can be a helpful tool in evaluating the involvement of the serotonin 2A receptor in the complex mechanisms of impulsive aggressive and anxious behaviour. The 5HT-2A binding index of the right frontal cortex appears to be a valid biomarker in differentiating the studied canine behavioural disorders.     

Neuro-imaging the serotonin 2A receptor as a valid biomarker for canine behavioural disorders

The serotonergic system is disturbed in different mood and affective disorders, with especially the serotonin (5-HT) 2A receptor involved in impulsive aggressiveness and anxiety. The aim of the study was to evaluate the involvement of the brain 5-HT 2A receptor in dogs with different behavioural disorders.Three groups of drug naive dogs were studied: 22 dogs showing impulsive aggressive behaviour, 22 showing normal behaviour, and 22 showing anxious behaviour. The serotonin 2A receptor was evaluated with Single Photon Emission Computed Tomography (SPECT) and the serotonin 2A receptor-selective radiopharmaceutical ¹²³I-R91150. A serotonin 2A receptor binding index (BI), proportional to the cortical receptor density, was calculated. A receiver operating characteristic (ROC) analysis was performed to determine cut-off values at which optimal sensitivity and specificity are achieved and to evaluate the general performance of the BI in reflecting the state of the dog, i.e., impulsive aggressive, normal or anxious.Significantly (P < 0.0056) altered 5-HT 2A receptor binding indices were found in bilateral frontal, temporal and occipital cortical brain areas of the dogs behaving abnormally, with consistently increased BI in impulsive aggressive dogs and decreased BI in anxious dogs. These results provide clear evidence for a disturbed serotonergic balance in canine impulsive aggression and anxiety disorders. A right frontal cut-off value of ⩾1.92 with 86.4% sensitivity and 2.3% (1-specificity) was obtained for the impulsive aggressive dogs. Differentiating the anxious dogs from the rest of the population was possible with a cut-off value of ⩽1.73 with 86.4% sensitivity and 18.2% (1-specificity).We conclude that SPECT imaging with the radioligand ¹²³I-R91150 can be a helpful tool in evaluating the involvement of the serotonin 2A receptor in the complex mechanisms of impulsive aggressive and anxious behaviour. The 5HT-2A binding index of the right frontal cortex appears to be a valid biomarker in differentiating the studied canine behavioural disorders.     

NDV对雏鸵鸟HPA轴的影响

以45日龄雏鸵鸟为试验动物,分正常组和攻毒组,利用RIA技术和TUNEL技术,探讨新城疫病毒（NDV）对雏鸵鸟HPA轴的影响。结果表明,雏鸵鸟感染NDV,HPA轴内细胞凋亡数量在病毒感染期间明显高于对照组,提示NDV能诱导雏鸵鸟HPA轴系统发生细胞凋亡;在病毒接种后1d,肾上腺内可检测到大量凋亡细胞,接种5d后凋亡数量显著增加（P〈0.05）,之后凋亡呈下降趋势,肾上腺内细胞凋亡的动态变化反映了雏鸵鸟HPA轴对ND病变的适应和调节。雏鸵鸟感染NDV,血清ACTH水平于NDV接种后1d开始上升,至5d达到峰值（P〈0.01）,之后有所下降,渐趋于正常;血清Cor水平于病毒接种后1d开始下降,至7d有所回升,9d渐趋于正常水平,表明NDV接种后雏鸵鸟血清ACTH和Cor水平的变化与其HPA轴功能的损伤及恢复密切相关。     

Differential serotonergic mediation of aggression in roosters bred for resistance and susceptibility to Marek’s disease

1. Serotonin (5-HT) is a primary regulating neurotransmitter involved in aggressive and impulsive behaviours in mammals. Previous studies have also demonstrated that the function of the serotonergic system in regulating aggression is affected by both genetic and environmental factors. The serotonergic system may display similar functions in chickens.

2. Our objective was to investigate the aggressive and impulsive behavioural response to antagonism of the 5-HT1A and 1B receptors in cocks bred for susceptibility and resistance to Marek’s disease (i.e. strain 7₂ and 6₃, respectively).

3. Cocks from strain 7₂ exhibited increased aggressive behaviours and lower brain 5-HT concentrations compared to strain 6₃ cocks.

4. Antagonism of 5-HT1A receptors increased aggressiveness and reduced serotonin turnover in strain 7₂, but not strain 6₃ cocks. 5-HT1B receptor antagonism had no effect on aggression or serotonin turnover in either strain.

5. Levels of the serotonin metabolite 5-HIAA, but not absolute central 5-HT levels, were altered in both strains following 5-HT1B antagonism, but only in strain 7₂ cocks following 5-HT1A antagonism.

6. The data suggest that 5-HT1A and 1B regulate aggression differently in high and low aggressive strains.     

Cortisol, adrenocorticotropic hormone, serotonin, adrenaline and noradrenaline serum concentrations in relation to disease and stress in the horse

No detailed comparative data are available on the hormonal parameters of horses suffering from a number of diseases. The aim of our study was to measure concentrations of cortisol, adrenocorticotropic hormone (ACTH), serotonin, adrenaline and noradrenaline in horses with various diseases and following surgery, to assess the response of the HPA axis and adrenal medulla. Blood samples were obtained from six groups of horses comprising a total of 119 animals as follows: laminitis, acute abdominal syndrome (AAS), castration surgery, acute diseases, chronic diseases and healthy controls. Serum hormonal concentrations were determined for each group for comparison. Statistically significant differences between all groups and controls were found for cortisol, ACTH (except for castration), serotonin and adrenaline concentrations but only in horses with laminitis and AAS for noradrenaline. No statistically significant differences were found between males and females. The largest changes in the pituitary-adrenal axis activity occurred mainly in acute diseases, laminitis and in the AAS group.     

Analysis of 1040 cases of canine aggression in a referral practice in Spain

A retrospective study was designed to assess the prevalence and clinical presentation of canine aggression problems in a referral practice in Spain. One thousand forty canine aggression cases seen at the Animal Behavior Clinic (Barcelona School of Veterinary Medicine) were analyzed. Each aggression problem was characterized according to 7 predefined diagnostic categories. Breed and sex-related risk factors were calculated by comparing the aggressive dogs to a control population. Aggression problems were the most common behavior complaint (52.28% of all canine behavior cases). Owner-directed aggression was the most frequent of the aggression complaints (38.55%), followed by aggression towards other dogs (34.85%) and unfamiliar people (21.95%). A mean of 1.4 diagnoses of aggression per dog were established. Social conflict aggression towards family members was the most common diagnostic category (35.34%). Sixty nine per cent of aggressive dogs were males and 31% were females, from which only 11 and 12 percent were neutered respectively. Two breeds, the English cocker spaniel and the Catalan sheepdog, presented a particularly high risk for aggression in the studied population.     

不同周龄蛋鸡攻击行为与五羟色胺、皮质酮的相关性分析

为探讨蛋鸡攻击行为与五羟色胺、皮质酮的相关性,选用1日龄京白939雏鸡96只,随机分为6个重复,每重复16只,采用瞬时观察法和连续观察法筛选不同周龄攻击行为有差异的蛋鸡,结合ELISA和qRT-PCR方法测定蛋鸡血清激素水平和5-HT1A受体mRNA表达量的变化。结果显示:蛋鸡的攻击行为随周龄的增加呈现逐渐上升的趋势(P<0.05);整体看,血清五羟色胺(5-HT)含量随周龄的增加呈下降趋势,皮质酮(CORT)呈现上升趋势(P<0.05),而下丘脑5-HT1A受体mRNA表达量随周龄增加有上升的趋势(P<0.05或P<0.01)。Pearson相关分析结果显示,蛋鸡攻击行为与血清五羟色胺(5-HT)呈极显著负相关(R=-0.741,P<0.01),与皮质酮(CORT)呈显著正相关(R=0.751,P<0.01)。综上所述,血清激素水平与蛋鸡攻击行为有一定联系,5-HT1A受体基因可能参与调控蛋鸡的攻击行为。     

Central administration of neuropeptide B, but not prolactin-releasing peptide, stimulates cortisol secretion in sheep

Two neuropeptides, neuropeptide B (NPB) and prolactin-releasing peptide (PrRP), have been suggested to play important roles in control of the hypothalamic-pituitary-adrenal (HPA) axis in rodents. The aim of the present study was to clarify the central actions of NPB or PrRP in sheep. Ovariectomized ewes were surgically implanted with a cannula directed to the lateral ventricle. They received intracerebroventricular (icv) administration of 400 mul of artificial cerebrospinal fluid, NPB (0.05, 0.5 or 5 nmol), PrRP (0.5, 5 or 50 nmol) or corticotropin-releasing hormone (CRH, 0.5 or 5 nmol) through the cannula, and blood samples were taken 30 and 0 min prior to and 15, 30, 60 and 90 min after the injection. Cortisol concentrations in plasma were determined by enzyme immunoassay. Administration of 0.5 nmol NPB resulted in a significant increase in the cortisol concentration compared with the vehicle control, whereas the cortisol concentration after lower or higher doses of NPB did not differ from the control value. Thus, an icv injection of NPB produced a bell-shaped dose-response of cortisol concentration. Administration of PrRP had no significant effect on the cortisol concentrations at any dose examined. Icv injection of CRH dose-dependently increased plasma cortisol concentrations. These results demonstrate that central NPB stimulates cortisol secretion, suggesting that this neuropeptide plays some roles in control of the HPA axis in sheep. On the other hand, unlike its role in rodents, PrRP is unlikely to be involved in control of the HPA axis in this species.     

氟西汀和5-羟色胺对肉鸡肺动脉平滑肌细胞增殖与凋亡的影响

为探讨5-羟色胺转载体(5-HTT)在肉鸡肺动脉高压综合征发病中的机制,采用MTT比色法、流式细胞术及Hoechst33258荧光染色法研究5-羟色胺(5-HT)和5-HTT抑制剂氟西汀对体外培养的肉鸡肺动脉平滑肌细胞(PASMC)增殖与凋亡的影响,发现氟西汀能够抑制5-HT促PASMC增殖的作用;氟西汀能明显促进PASMC的凋亡,但氟西汀和5-HT共同作用于细胞,PASMC凋亡率明显少于氟西汀单独处理组。表明5-HTT在调节肉鸡PASMC的增殖和凋亡方面起重要作用,有可能参与肺动脉高压肉鸡肺血管重构的形成。     

Relationship between the serum concentrations of serotonin and lipids and aggression in dogs

The serum concentrations of serotonin and lipids--triglycerides, total cholesterol, low density lipoprotein, high density lipoprotein and very low density lipoprotein--were determined in 18 normal dogs and 23 dogs diagnosed as aggressive on the basis of interviews with their owners and an assessment of their behaviour with reference to a canine overt aggression chart. The serum serotonin levels in the aggressive dogs were significantly lower than in the normal dogs (P<0.01), but the differences in serum lipids between the two groups were not statistically significant.     

Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Hospitalized Neonatal Foals

Background: Transient hypothalamic-pituitary-adrenal (HPA) axis dysfunction occurs frequently in critically ill humans and impacts survival. The prevalence and impact of HPA axis dysfunction in critically ill neonatal foals are not well characterized.
Hypotheses: (1) HPA axis dysfunction occurs in hospitalized neonatal foals, and is characterized by inappropriately low basal serum cortisol concentration or inadequate cortisol response to exogenous adrenocorticotropic hormone (ACTH); (2) hospitalized foals with HPA axis dysfunction have more severe disease and are less likely to survive than hospitalized foals with normal HPA axis function.
Animals: Seventy-two hospitalized foals and 23 healthy age-matched foals.
Methods: Basal ACTH and cortisol concentrations were measured and a paired low-dose (10 μg)/high-dose (100 μg) cosyntropin stimulation test was performed at admission in hospitalized foals. HPA axis dysfunction was defined as (1) an inappropriately low basal cortisol concentration or (2) an inadequate increase in cortisol concentration (delta cortisol) after administration of cosyntropin, with cut-off values for appropriate basal and delta cortisol concentrations determined from results obtained in healthy age-matched foals.
Results: Forty-six percent of hospitalized foals had an inappropriately low basal cortisol concentration and 52% had an inadequate delta cortisol concentration after administration of the 100 μg dose of cosyntropin. An inadequate delta cortisol response to the high (100 μg) dose of cosyntropin was significantly correlated with shock and multiple organ dysfunction syndrome in hospitalized foals, and with decreased survival in a subgroup of septic foals.
Conclusions and Clinical Importance: HPA axis dysfunction occurs frequently in hospitalized neonatal foals, and negatively impacts disease severity and survival.     

Incidence of and risk factors for cat bites: a first step in prevention and treatment of feline aggression

Feline aggression towards people has a smaller incidence than canine aggression, but also represents an important public health problem. The aim of this work was to analyse feline aggression reported towards people, to estimate its incidence and to assess the risk factors involved. The information was obtained from the Public Health Centres in the Valencian Region (Spain). A total of 936 acts of feline aggression were analysed. Cats inflicted 8% of all animal bites reported. The annual average was 6.36 feline aggression incidents per 100,000 people. Most aggressive incidents occurred during the summer months. Children (0-14 years old) and women were more likely to be bitten. Wounds were mainly punctures, single, and mild, and were located mostly on the hands. In children, the head and neck areas were affected much more than in adults. The cats involved in incidents were mostly Siamese, female and owned; these cats mainly attacked their owners. Most occurrences were a defensive response by the cat.     

Hypothalamic-pituitary-adrenal axis responsiveness to insulin-induced hypoglycaemia is modified by trypanosome infection in Boran (Bos indicus) cattle.

Ten Boran (Bos indicus) cattle were used to study the stress responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis during trypanosome infection. Five cattle were infected with Trypanosoma congolense IL 1180 by tsetse challenge and five cattle served as controls. All infected animals developed acute trypanosomiasis. Insulin-induced hypoglycaemia (50 per cent of pre-insulin glucose concentration) was used as a stress factor. Acute hypoglycaemia was observed in three infected and three control animals after insulin challenge. Two animals from each group either did not respond or responded slowly. Hypoglycaemia in infected animals completely failed to induce an HPA axis response, while in control animals an HPA axis response was indicated by a significant increase in plasma adrenocorticotrophic hormone (ACTH) and cortisol concentrations (P less than 0.01). The results show that trypanosomiasis in Boran cattle can cause a decrease in the stress responsiveness of the HPA axis as indicated by a blunted ACTH/cortisol response to insulin-induced hypoglycaemia.     

Effects of a program of human interaction and alterations in diet composition on activity of the hypothalamic-pituitary-adrenal axis in dogs housed in a public animal shelter

OBJECTIVE: To determine whether a program of human interaction or alterations in diet composition would alter activity of the hypothalamic-pituitary-adrenal (HPA) axis in dogs housed in an animal shelter. DESIGN: Prospective study. ANIMALS: 40 dogs. PROCEDURE: Dogs were (n = 20) or were not (20) enrolled in a program of regular supplemental human interaction (20 min/d, 5 d/wk, for 8 weeks) involving stroking, massaging, and behavioral training. In addition, half the dogs in each group were fed a typical maintenance-type diet, and the other half were fed a premium diet. Plasma cortisol and ACTH concentrations were measured during weeks 0, 2, 4, and 8 and before and after exposure to a battery of novel situations during weeks 0 and 8. RESULTS: Plasma cortisol concentration was significantly decreased by week 2, but plasma ACTH concentration was not significantly decreased until week 8 and then only in dogs fed the premium diet. Following exposure to novel situations, plasma cortisol and ACTH concentrations were significantly increased. However, during week 8, dogs enrolled in the program of human interaction had significantly lower increases in cortisol concentration than did dogs not enrolled in the program. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that both a program of human interaction and alterations in diet composition have moderating effects on activity of the HPA axis in dogs housed in an animal shelter and that activity of the HPA axis may be increased for a longer period during shelter housing than measurement of plasma cortisol concentration alone would suggest.     

Hypothalamic-Pituitary-Adrenal Axis Assessment in Healthy Term Neonatal Foals Utilizing a Paired Low Dose/High Dose ACTH Stimulation Test

Background: Hypothalamic-pituitary-adrenal (HPA) axis function is dynamic in the neonatal foal. The paired low dose/high dose cosyntropin (ACTH) stimulation test allows comprehensive HPA axis assessment, but has not been evaluated in neonatal foals.
Hypothesis: Foal age will significantly affect cortisol responses to a paired 10 and 100 μg dose cosyntropin stimulation test in healthy neonatal foals.
Animals: Twenty healthy neonatal foals.
Methods: HPA axis function was assessed in 12 foals at birth and at 12–24, 36–48 hours, and 5–7 days of age. At each age, basal cortisol and ACTH concentrations were measured and cortisol responses to 10 and 100 μg cosyntropin were assessed with a paired ACTH stimulation test protocol. Eight additional 36–48-hour-old foals received saline instead of 10 μg cosyntropin in the same-paired ACTH stimulation test design.
Results: At birth, foals had significantly higher basal cortisol and ACTH concentrations and higher basal ACTH : cortisol ratios compared with foals in all other age groups. A significant cortisol response to both the 10 and 100 μg doses of cosyntropin was observed in all foals. The magnitude of the cortisol response to both doses of cosyntropin was significantly different across age groups, with the most marked responses in younger foals. There was no effect of the paired ACTH stimulation test design itself on cortisol responses.
Conclusions and Clinical Importance: A paired 10 and 100 μg cosyntropin stimulation test can be used to evaluate HPA axis function in neonatal foals. Consideration of foal age is important in interpretation of HPA axis assessment.     

Differences in serotonin serum concentration between aggressive English cocker spaniels and aggressive dogs of other breeds

Aggression is one of the most common behavioral problems in dogs and may have important negative effects on public health, human–animal bond, and animal welfare. There is ample evidence showing a negative correlation between serum serotonin concentration and aggressive behavior in a variety of species, including the domestic dogs. This negative correlation is particularly pronounced in dogs that show impulsive aggression. Data obtained in some previous studies suggest that the English cocker spaniel (ECS) is more likely to show impulsive aggression than other breeds. Therefore, the aim of this study was to analyze possible differences in serum serotonin levels between aggressive ECS and aggressive dogs of other breeds. Nineteen ECSs presented for aggression at the Animal Behavior Service (School of Veterinary Science, Barcelona, Spain) were evaluated and compared with 20 aggressive dogs of other breeds attended at the same center. Serum serotonin levels were measured using an enzyme-linked immunosorbent assay method. Statistical analysis was done using the SPSS 15.0 for Windows. Aggressive ECSs had significantly (P < 0.001) lower levels of serum serotonin than aggressive dogs of other breeds (318.6 ± 67.1 and 852.77 ± 100.58 ng/mL, respectively). Variances were not significantly different between ECSs and other breeds (standard deviation = 449.84 ng/mL vs. 292.47 ng/mL, P > 0.05). This finding may explain why ECSs are more likely to show impulsive aggression than other breeds, and suggests that the ECS could be a good model to study the neurophysiologic mechanisms underlying impulsive aggression.     

Food intake and rumen motility in dwarf goats. Effects of some serotonin receptor agonists and antagonists

The serotonergic regulation of feeding behaviour has not so far been studied in ruminants. Therefore, the effects of some serotonin (5-HT) receptor agonists and antagonists on food intake and forestomach motility were studied in dwarf goats.Goats ate less food when treated intravenously (IV) with the 5-HT precursor 5-HTP (25 µg, 50 µg or 100 µg kg^–1 min^–1 over 15 min) than when they were treated with 5-HT (which does not pass the blood-brain barrier) or with saline. Accordingly, IV dexfenfluramine infusions (50 µg or 100 µg kg^–1 min^–1 over 15 min), which induces release of brain 5-HT, also led to dose-related reductions in food intake. In contrast, no anorectic effects were observed after IV infusions with the selective 5-HT reuptake inhibitor fluoxetine (100 µg kg^–1 min^–1 over 15 min), the selective 5-HT1A agonist 8-OH-DPAT (0.5 µg kg^–1 min^–1 over 15 min), or eltoprazine (4 or 8 µg kg^–1 min^–1 over 15 min), a mixed 5-HT1A/5HT1B receptor agonist. None of the 5-HT antagonists tested gave any increase in food consumption in this model. Interestingly, the non-selective 5-HT receptor antagonist methysergide (360 µg/kg IV) reduced food intake. This effect was most noticeable at 3 h after injection. The 5-HT3 receptor antagonist ondansetron (IV 10 µg kg^–1 min^–1 over 15 min) and the peripheral 5-HT2 receptor antagonist xylamidine (IV 100 µg kg^–1 min^–1 over 10 min) failed to modify food intake. These results provide evidence for central serotonergic involvement in the control of feeding. However, this control system differs markedly in goats and rodents.Dexfenfluramine, 5-HTP and eltoprazine administered at similar dose rates to those used in the food intake experiments induced some clinical signs including inhibition of forestomach contractions. These results, together with our earlierin vivo andin vitro observations, suggest that the inhibitory effects of serotonin receptor agonists on forestomach contractions are due to interactions with both peripheral and central serotonergic receptors. The change in smooth muscle tension, which leads to a change in the signals transmitted via vagal afferents to the central nervous system, appears not to modify feeding behaviour in dwarf goats.     

Effects of dermal dexamethasone application on ACTH and both basal and ACTH-stimulated cortisol concentration in normal horses

There are no data available regarding the systemic (adverse) effects which might be induced by topical/dermal glucocorticoids (GCs) application in the horse. Besides their widespread use for the treatment of a variety of peripheral inflammatory disorders such as atopic dermatitis, eczemas or arthritis in the horse, their surreptitious application has become a concern in doping cases in competition/performance horses. Assessing both basal and ACTH‐stimulated plasma cortisol as well as basal ACTH concentrations following application of dexamethsone‐containing dermal ointment is necessary to determine influences on hypothalamus‐pituitary‐adrenal (HPA) axis. Ten clinically healthy adult standardbred horses (6 mares, 4 geldings) were rubbed twice daily each with 50 g dexamethasone‐containing ointment on a defined skin area (30 × 50 cm) for 10 days. RIA and chemiluminescent enzyme immuno‐metric assay were used to determine resting and ACTH‐stimulated plasma cortisol and basal ACTH concentrations, respectively. HPA feedback sensitivity and adrenal function were measured by a standard ACTH stimulation test. Dermal dexamethasone suppressed significantly the resting plasma cortisol level (to 75–98%) below baseline (P < 0.001) within the first 2 days and decreased further until day 10. ACTH stimulation test showed a markedly reduced rise in plasma cortisol concentrations (P < 0.001 vs. baseline). Plasma ACTH level decreased also during topical dexamethasone application. The number of total lymphocytes and eosinophil granulocytes was reduced, whereas the number of neutrophils increased. No significant change of serum biochemical parameters was noted. Dermal dexamethasone application has the potential to cause an almost complete and transient HPA axis suppression and altered leukocyte distribution in normal horses. The effects on HPA axis function should be considered in relation to the inability of animals to resist stress situations. The data further implicate that percutaneously absorbed dexamethasone (GCs) may cause systemic effects relevant to ‘doping’.     

Association study of molecular polymorphisms in candidate genes related to stress responses with production and meat quality traits in pigs

The hypothalamic-pituitary-adrenal (HPA) axis exerts a large range of effects on metabolism, the immune system, inflammatory processes, and brain functions. Together with the sympathetic nervous system, it is also the most important stress-responsive neuroendocrine system. Both systems influence production traits, carcass composition, and meat quality. The HPA axis may be a critical target for genetic selection of more robust animals. Indeed, numerous studies in various species have demonstrated the importance of genetic factors in shaping the individual HPA axis phenotype, and genetic polymorphism can be found at each level of the axis, including hormone production by the adrenal cortices under stimulation by adrenocorticotropic hormone (ACTH), hormone bioavailability, or receptor and postreceptor mechanisms. The aim of the present experiment was to extend these findings to the brain neurochemical systems involved in stress responses. To this end, a number of candidate genes were sequenced for molecular polymorphisms and their association was studied with stress neuroendocrine and production traits in a genetically diverse population consisting of 100 female pigs from an advanced intercross (F10-F12) between 2 highly divergent breeds, Large White (LW) and Meishan (MS). The LW breed has a high production potential for lean meat and a low HPA axis activity, and the MS breed has low growth rate, fat carcasses—but large litters of highly viable piglets—and a high HPA axis activity. Candidate genes were chosen in the catecholaminergic and serotonergic pathways, in the pituitary control of cortisol production, among genes previously demonstrated to be differentially expressed in ACTH-stimulated adrenal glands from LW and MS pigs, and in cortisol receptors. Sixty new polymorphisms were found. The association study with carcass and meat quality traits and with endocrine traits showed a number of significant results, such as monoamine oxidase (MAOA) polymorphisms with growth rate (P = 0.01); lean content and intramuscular fat (P < 0.01), which are the most important traits for carcass value; dopamine receptor D3 (DRD3) with carcass composition (P < 0.05); and vasopressin receptor 1B (AVPR1B) with meat quality traits (P ≤ 0.05). The effect of these polymorphisms on neuroendocrine parameters (eg DRD3 and HPA axis or AVPR1B and catecholamines) indicates information regarding their biological mechanism of action.