Self-grooming Behavior Research Articles

Perinatal fluoxetine exposure changes social and stress-coping behavior in adult rats housed in a seminatural environment

The use of selective serotonin reuptake inhibitors (SSRI) during pregnancy has increased tremendously, but the consequences for the offspring remain largely unclear. Several studies have described potential effects of perinatal SSRI-exposure on neurobehavioral outcomes using simplified rodent test set-ups, however these set-ups only assess a small fraction of the behavior. For translational purposes it is important to take the environmental influences into account which children are exposed to in real life. By using a seminatural environmental set-up, this study is the first to assess behavioral outcomes in offspring exposed to perinatal SSRI exposure under seminatural circumstances. Mothers received daily the SSRI fluoxetine (FLX, 10 mg/kg p.o.) or vehicle (CTR) from gestational day 1 until postnatal day 21. To assess the effect of FLX exposure during early development, female and male offspring were behaviorally tested in the seminatural environment at adulthood. Baseline behavior was measured in addition to responses during and after stressful white-noise events. Behavior was observed on two days, day 4 on which females were sexually non-receptive, and day 7, on which females were sexual receptive. Perinatal FLX exposure reduced general activity in females and increased behavior related to a social context in both males and females. After a stressful white-noise event some behaviors switched. Whereas FLX-females switch from resting socially to resting more solitarily, FLX-males show an increase in self-grooming behavior after the stressor and showed more freezing behavior in the open area. We conclude that perinatal FLX exposure leads to alterations in social and stress-coping behaviors in adulthood, when observed in a seminatural environment. Whether these adaptations in behavior are advantageous or disadvantageous remains to be established.

Effects of sublethal doses of clothianidin and/or V. destructor on honey bee (Apis mellifera) self-grooming behavior and associated gene expression

Little is known about the combined effects of stressors on social immunity of honey bees (Apis mellifera) and related gene expression. The interaction between sublethal doses of a neurotoxin, clothianidin, and the ectoparasite, Varroa destructor, was examined by measuring differentially expressed genes (DEGs) in brains, deformed wing virus (DWV) and the proportion and intensity of self-grooming. Evidence for an interaction was observed between the stressors in a reduction in the proportion of intense groomers. Only the lowest dose of clothianidin alone reduced the proportion of self-groomers and increased DWV levels. V. destructor shared a higher proportion of DEGs with the combined stressors compared to clothianidin, indicating that the effects of V. destructor were more pervasive than those of clothianidin when they were combined. The number of up-regulated DEGs were reduced with the combined stressors compared to clothianidin alone, suggesting an interference with the impacts of clothianidin. Clothianidin and V. destructor affected DEGs from different biological pathways but shared impacts on pathways related to neurodegenerative disorders, like Alzheimer’s, which could be related to neurological dysfunction and may explain their negative impacts on grooming. This study shows that the combination of clothianidin and V. destructor resulted in a complex and non-additive interaction.

Effects of Cacna1c haploinsufficiency on social interaction behavior and 50-kHz ultrasonic vocalizations in adult female rats

The risk gene CACNA1C is strongly implicated in the etiology of all major psychiatric disorders, such as depressive disorder, bipolar disorder, autism spectrum disorder, and schizophrenia. These disorders feature high levels of comorbidity and share an overlap of symptoms; in particular, deficits in social functioning are common. Intriguingly, sex-dependent effects of CACNA1C single nucleotide polymorphisms on prevalence, health outcomes, and psychological traits have been reported, typically suggesting that women are more affected by CACNA1C mutations than men. In rodents, genetic modifications specifically targeting Cacna1c have repeatedly been linked to deficits in social behavior in male mice and rats but many studies neglect the sex-dependent effects observed in humans. Our study focused on the role of Cacna1c in regulating social behavior and communication in adult female rats. We compared social and non-social behavior together with concomitant emission of pro-social 50-kHz ultrasonic vocalizations (USV) associated with positive affect in constitutive heterozygous (Cacna1c+/−) rats to wildtype (Cacna1c+/+) littermate controls. Our results indicate that partial Cacna1c depletion leads to strongly reduced emission of 50-kHz USV and mild social deficits during female direct reciprocal social interaction. Detailed temporal analyses revealed most prominent reductions of 50-kHz USV during non-social behavior, suggesting that reduced positive affect occurs in a social context in Cacna1c+/− rats but is not specifically linked to social behavior. Finally, we observed increased self-grooming behavior in Cacna1c+/− rats, consistent with an autism-like phenotype. Our findings in rats thus support a role of Cacna1c in regulating behavioral phenotypes with relevance for several neuropsychiatric disorders.

The Effect of ASIC3 Knockout on Corticostriatal Circuit and Mouse Self-grooming Behavior.

Stereotypic and/or repetitive behavior is one of the major symptoms of autism spectrum disorder (ASD). Increase of self-grooming behavior is a behavioral phenotype commonly observed in the mouse models for ASD. Previously, we have shown that knockout of acid-sensing ion channel 3 (ASIC3) led to the increased self-grooming behavior in resident-intruder test. Given the facts that ASIC3 is mainly expressed in the peripheral dorsal root ganglion (DRG) and conditional knockout of ASIC3 in the proprioceptors induced proprioception deficits. We speculate a hypothesis that stereotypic phenotype related to ASD, pararalled with striatal dysfunction, might be caused by proprioception defect in the peripheral sensory neuron origin. Herein, we investigate in depth whether and how ASIC3 is involved in the regulation of self-grooming behavior. First, we observed that Asic3 null mutant mice exhibited increased self-grooming in social interaction during juvenile stage. Similarly, they displayed increased self-grooming behavior in a novel cage in the absence of cagemate. To further understand the mechanism by which ASIC3 affects grooming behavior, we analyzed neurochemical, neuropathological and electrophysiological features in the dorsal striatum of Asic3 null mutant mice. Knockout of Asic3 increased dopamine (DA) activity and phospho-ERK immunoreactivities in the dorsal striatum. Furthermore, we detected a lower paired-pulse ratio (PPR) and impaired long-term potentiation (LTP) in corticostriatal circuits in Asic3 null mutant mice as compared with wild-type (WT) littermates. Moreover, knockout of Asic3 altered the medial spiny neurons in the striatum with defects in presynaptic function and decrease of dendritic spines. Lastly, genetic ablation of Asic3 specifically in parvalbumin-positive (PV+) cells resulted in the increase of self-grooming behavior in mice. These findings suggest knockout of Asic3 in the PV+ neurons alters grooming behavior by co-opting corticostriatal circuits.

Kami-shoyo-san ameliorates sociability deficits in ovariectomized mice, a putative female model of autism spectrum disorder, via facilitating dopamine D1 and GABAA receptor functions

Ethnopharmacological relevanceKami-shoyo-san (KSS) is a Kampo formula used clinically for menopause-related symptoms in Japan. However, the effect of KSS on autism spectrum disorder (ASD), a developmental disorder with a higher prevalence in males than in females, has not been reported yet. Aim of the studyIt is accepted generally that dysfunction in the GABAergic system is associated with pathogenesis of ASD. In our previous study, a decrease in brain allopregnanolone (ALLO), a positive allosteric GABAA receptor modulator, induced ASD-like symptoms such as impaired sociability-related performance and increased repetitive self-grooming behavior in male mice, and that KSS ameliorated these behavioral abnormalities via GABAA receptor- and dopamine D1 receptor-mediated mechanisms. In this study, to better understand a gender difference in the prevalence of ASD, we examined whether dissection of ovary (OVX), a major organ secreting progesterone in females, causes ASD-like behaviors in a manner dependent on brain ALLO levels, and if so, how KSS affects the behaviors. Materials and methodsSix-week-old ICR female mice received ovariectomy, and KSS (74 mg/kg and 222 mg/kg, p.o.) were treated before 1 h starting each behavioral test. The sociability, social anxiety-like behavior, and self-grooming behavior were analyzed by the resident-intruder test, mirror chamber test, and open field test, respectively. After finishing the behavioral experiment, the ALLO content in the brain was measured by ELISA. Furthermore, we examined the effects of OVX on the neuro-signaling pathways in the prefrontal cortex and striatum by Western blotting. ResultsThe results revealed that OVX induced sociability deficits and social anxiety-related behaviors, but not repetitive self-grooming behavior, and that these behavioral changes were accompanied not only by a decrease of brain ALLO levels, but also by impairment of CREB- and CaMKIIα-mediated neuro-signaling in the prefrontal cortex. Moreover, the administration of KSS had no effect on the brain ALLO level, but significantly ameliorated the OVX-induced behavioral and neurochemical changes via facilitation of GABAA receptor and dopamine D1 receptor-mediated neurotransmission. ConclusionsThese findings suggest that a decrease in gonadal hormone-derived ALLO plays a major role in ASD-like behaviors in female mice and that KSS is beneficial for the treatment of ASD in females.

Spatial memory formation requires netrin-1 expression by neurons in the adult mammalian brain.

Netrin-1 was initially characterized as an axon guidance molecule that is essential for normal embryonic neural development; however, many types of neurons continue to express netrin-1 in the postnatal and adult mammalian brain. Netrin-1 and the netrin receptor DCC are both enriched at synapses. In the adult hippocampus, activity-dependent secretion of netrin-1 by neurons potentiates glutamatergic synapse function, and is critical for long-term potentiation, an experimental cellular model of learning and memory. Here, we assessed the impact of neuronal expression of netrin-1 in the adult brain on behavior using tests of learning and memory. We show that adult mice exhibit impaired spatial memory following conditional deletion of netrin-1 from glutamatergic neurons in the hippocampus and neocortex. Further, we provide evidence that mice with conditional deletion of netrin-1 do not display aberrant anxiety-like phenotypes and show a reduction in self-grooming behavior. These findings reveal a critical role for netrin-1 expressed by neurons in the regulation of spatial memory formation.

Characterizing grooming behavior patterns and the influence of brush access on the behavior of group-housed dairy calves

Group housing allows for dairy calves to perform social grooming behavior; however, the use of mechanical brushes may influence how calves groom themselves and others. Our objectives were, first, to characterize the bout characteristics of brush use, self-grooming, and allogrooming in calves and, second, to evaluate the effects of access to a rotating brush on grooming behavior. Holstein heifer and bull calves (n = 32) were group-housed (4 calves/group) at 2 wk of life (17 ± 3 d of age; mean ± standard deviation) and followed to wk 7 of life. Pens were assigned to receive either a rotating brush (BR; n = 4 pens) or no brush (CON; n = 4 pens). Behavior was recorded continuously for 12 h for 2 focal calves/pen on 2 d during wk 4, 6, and 7 of life. We performed a bout analysis by fitting a mixture of normal distributions to the log10-transformed frequency distribution of the intervals between recorded periods of behavior. We calculated bout criteria for brush use (125.9 s), allogrooming (125.9 s), and self-grooming (a mixture of 3 normal distributions provided the best fit for these data, providing 2 bout criteria: a shorter (micro) bout criterion of 50.1 s and a longer (macro) criterion of 1,000 s). Brush use was consistent across weeks, and calves used the brush for 20.5 ± 6.1 min/12 h observation period, in 31.1 ± 1.7 bouts (mean ± SE). The frequency and duration of allogrooming bouts did not differ between treatments and across time. The BR calves tended to self-groom more than CON calves (16.3 vs. 14.3 min/12 h; BR vs. CON; SE = 0.68), and time spent self-grooming decreased across weeks. The frequency and duration of self-grooming micro bouts did not differ between treatments, but BR calves had shorter, more frequent self-grooming macro bouts (10.58 vs. 9.46 bouts; BR vs. CON; SE = 0.24). In summary, we determined that bout criteria could be fitted to grooming behaviors, which may be useful when characterizing these behaviors in future work, and that providing access to a rotating brush influenced self-grooming behavior in group-housed calves.

Camphor, Applied Epidermally to the Back, Causes Snout- and Chest-Grooming in Rats: A Response Mediated by Cutaneous TRP Channels.

Thermoregulatory grooming, a behavioral defense against heat, is known to be driven by skin-temperature signals. Because at least some thermal cutaneous signals that drive heat defenses are likely to be generated by transient receptor potential (TRP) channels, we hypothesized that warmth-sensitive TRPs drive thermoregulatory grooming. Adult male Wistar rats were used. We showed that camphor, a nonselective agonist of several TRP channels, including vanilloid (V) 3, when applied epidermally to the back (500 mg/kg), caused a pronounced self-grooming response, including paw-licking and snout- and chest-“washing”. By the percentage of time spent grooming, the response was similar to the thermoregulatory grooming observed during exposure to ambient warmth (32 °C). Ruthenium red (a non-selective antagonist of TRP channels, including TRPV3), when administered intravenously at a dose of 0.1 mg/kg, attenuated the self-grooming behavior induced by either ambient warmth or epidermal camphor. Furthermore, the intravenous administration of AMG8432 (40 mg/kg), a relatively selective TRPV3 antagonist, also attenuated the self-grooming response to epidermal camphor. We conclude that camphor causes the self-grooming behavior by acting on TRP channels in the skin. We propose that cutaneous warmth signals mediated by TRP channels, possibly including TRPV3, drive thermoregulatory self-grooming in rats.

Kami-shoyo-san improves ASD-like behaviors caused by decreasing allopregnanolone biosynthesis in an SKF mouse model of autism.

Dysfunctions in the GABAergic system are associated with the pathogenesis of autism spectrum disorder (ASD). However, the mechanisms by which GABAergic system dysfunctions induce the pathophysiology of ASD remain unclear. We previously demonstrated that a selective type I 5α-reductase inhibitor SKF105111 (SKF) induced ASD-like behaviors, such as impaired sociability-related performance and repetitive grooming behaviors, in male mice. Moreover, the effects of SKF were caused by a decrease in the endogenous levels of allopregnanolone (ALLO), a positive allosteric modulator of the GABAA receptor. In this study, we used SKF-treated male mice as a putative animal model of ASD and examined the effects of Kami-shoyo-san (KSS) as an experimental therapeutic strategy for ASD. KSS is a traditional Kampo formula consisting of 10 different crude drugs and has been used for the treatment of neuropsychiatric symptoms. KSS dose-dependently attenuated sociability deficits and suppressed an increase in grooming behaviors in SKF-treated mice without affecting ALLO content in the prefrontal cortex. The systemic administration of the dopamine D1 receptor antagonist SCH23390 reversed the ameliorative effects of KSS. On the other hand, the dopamine D2 receptor antagonist sulpiride and GABAA receptor antagonist bicuculline only attenuated the ameliorative effect of KSS on repetitive self-grooming behaviors. The present results indicate that KSS improves SKF-induced ASD-like behaviors by facilitating dopamine receptor-mediated mechanisms and partly by neurosteroid-independent GABAA receptor-mediated neurotransmission. Therefore, KSS is a potential candidate for the treatment of ASD.

Minocycline ameliorates anxiety-related self-grooming behaviors and alters hippocampal neuroinflammation, GABA and serum cholesterol levels in female Sprague-Dawley rats subjected to chronic unpredictable mild stress

Neuroinflammation induced by stress results in aberrant neurotransmission and dyslipidemia, which can trigger depression- and anxiety-like behaviors. Gamma-aminobutyric acid (GABA) and cholesterol play a crucial role in anxiety-like states, including self-grooming - a common stress-evoked rodent behavior. However, the interaction between neuroinflammation, GABA and cholesterol under stress, and their effects on grooming, remain unclear. Here, we utilize the chronic unpredictable mild stress (CUMS) rat cohort used previously in our Zhang et al. (2019) study, to examine whether CUMS affects grooming behavior, and whether minocycline, a microglia antagonist, can correct these behavioral deficits, accompanied by altering hippocampal neuroinflammation, GABA and serum cholesterol levels. Female Sprague-Dawley rats underwent a 6-week CUMS and received daily minocycline (40 mg/kg, i.p.) during this period, followed by behavioral testing in the open field test. Serum cholesterol, inflammatory cytokines and GABA levels in hippocampus were assayed by ELISA. CUMS significantly decreased locomotion, rearing, central zone entries and time spent in the open field center compared to unstressed controls. CUMS also strongly affected self-grooming behaviors, increasing the frequency of grooming episodes, the number of transitions, interruptions and individual elements of various grooming phases. However, these CUMS-induced behavioral abnormalities were corrected by minocycline. Likewise, CUMS elevated total serum cholesterol and lowered serum high-density lipoprotein cholesterol, whereas minocycline ameliorated these responses. CUMS also lowered hippocampal GABA, whereas minocycline normalized CUMS-induced GABA in the hippocampus. We also found significant correlations between neuroinflammation and GABA, neuroinflammation and cholesterol, GABA and grooming, as well as cholesterol and grooming measures, further implicating stress-evoked neuroinflammation, GABA and cholesterol in the regulation of complex rodent behaviors. In summary, minocycline ameliorated CUMS-induced aberrant self-grooming behaviors in rats by altering hippocampal neuroinflammation, GABA and serum cholesterol levels.

Level of stress in relation to emotional reactivity of hens

The aim of the study was to associate behavioural reactions of laying hens with the level of stress and to answer the question whether it is possible to select reactions that will facilitate phenotypic assessment of the level of stress in these birds. The investigations were carried out in 50 Green-legged Partridge, 50 Polbar and 50 Leghorn birds. A modified open-field test (MOFT) and a tonic immobility test were applied. Next, the quality of feathers was evaluated and the level of corticosterone in the feathers was determined. The corticosterone level was assessed in relation to the genetic group and feather quality and in relation to the probability of the presence/absence of specific physiological–behavioural reactions. The analysis of the results revealed no correlations between the corticosterone level in the feathers and the quality of the feathers. In turn, there was a correlation between the hen breed and the corticosterone level in the feathers: a significant difference was found between Zk and Pb hens. It was demonstrated that the corticosterone level was significantly higher in birds that exhibited such behaviours as preening in the open-field test. To sum up the results, it can be concluded that such behaviours as feather preening and latency until tonic immobility occurs can be indicators of stress in laying hens.HighlightsThere was a correlation between the breed and the corticosterone level in the feathers: there was a significant difference between the Green-legged Partridge (3.97 ± 0.17) and Polbar (4.50 ± 0.19) hens.No significant correlations were found between the corticosterone level and the behavioural reactivity in the analysed hens.It was demonstrated that the corticosterone level was significantly higher in birds that exhibited self-grooming behaviours in the open-field test (4.61) than in hens that did not show such behaviours (3.91).

A rat model to study maternal depression during pregnancy and postpartum periods, its comorbidity with cardiovascular diseases and neurodevelopmental impact in the offspring

This study aimed to develop an animal model of human depression during pregnancy and lactation to examine the effect of maternal, perinatal depression on offspring development. Maternal depression during pregnancy affects up to 20% of women and is a risk factor for both the developmental and long-term health issues. It is often comorbid with the cardiovascular disease (CVD) that affects the uteroplacental circulation and impacts offspring development. More than half of the expecting mothers with depression use antidepressants that cross the placenta and may interfere with the neurodevelopmental programming. Thus, depressed pregnant mothers face a difficult choice whether “to use or not to use” antidepressant therapy, since both untreated depression and antenatal antidepressant exposure present increased risks of neurodevelopmental pathologies. The ongoing clinical debate presents inconclusive data, while the existing animal models of maternal depression do not include early gestational periods, and, do not monitor depressive-like behavior nor address the cardiovascular abnormalities. The presented model includes pregestational depressive behavior extending into pregnancy and lactation, periods that have not been previously examined. Rat dams exposed to pre-gestational chronic mild stress (CMS) developed a sustained decrease in self-grooming behavior, correlated with hormonal, behavioral, and cardiac changes persisting through the postpartum period. Preliminary data indicate neurodevelopmental delays, behavioral and cardiac abnormalities, and altered levels of both the brain and the heart markers in the offspring of stressed dams. Furthermore, the preliminary data predict that maternal pregnancy during the perinatal period is likely to impact the neurodevelopmental process in a sex-dependent manner. Thus the presented here model (PG-LAC CMS) fulfills both the face and the construct validity criteria for maternal stress-induced depression during pregnancy and postpartum that may facilitate further studies of the relative risks of untreated vs. antidepressant-treated maternal depression during pregnancy to the mother and her offspring.

Familiarity modulates social approach toward stressed conspecifics in female rats.

Familiarity between conspecifics may influence how social affective cues shape social behaviors. In a social affective preference test, experimental rats, when given the choice to explore an unfamiliar stressed or a naive adult, will avoid interaction with a stressed conspecific. To determine if familiarity would influence social interactions with stressed conspecifics, male and female test rats underwent 2 social affective preference tests in isosexual triads where an experimental rat was presented with a naïve and a stressed target conspecific who were either familiar (cagemate) or unfamiliar. Male and female experimental rats avoided stressed unfamiliar conspecifics. However, experimental female rats demonstrated a preference to interact with their stressed, familiar cagemates. Male and female rats exhibited more self-grooming and immobility behavior in the presence of stressed conspecifics, which may indicate emotion contagion. These findings suggest a sex-specific role of familiarity in social approach and avoidance, and warrant further mechanistic exploration.

Mice exposure to haloxyfop-p-methyl ester at predicted environmentally relevant concentrations leads to anti-predatory response deficit.

Although the efficiency of haloxyfop-p-methyl ester (HPME) as selective herbicide is acknowledged, its impact on non-target organisms is poorly known. It is not known whether the short exposure of mammals to low HPME concentrations (consistent with a realistic contamination scenario) poses risks to these animals. Thus, the aim of the current study is to evaluate the effects of HPME on the anti-predatory behavior of female Swiss mice exposed to it. The animals were divided in groups: non-exposed (control) and exposed (route: i.p., for 2days) to different herbicide concentrations (2.7 × 10-4g/kg and 2.7 × 10-2g/kg of body weight), which were considered environmentally relevant predicted concentrations. The animals were subjected to the open field and elevated plus-maze tests; results showed that the HPME did not lead to anxiolytic or anxiety behavior, or to locomotive changes in the tested animals, fact that was confirmed through the Basso Mouse Scale for locomotion scores. On the other hand, animals exposed to the herbicide were incapable of recognizing the snake as potential predator. Animals in the control group, exposed to a real snake (Pantherophis guttatus) remained longer in the safety zone of the test device, presented lower frequency of self-grooming behaviors for a shorter period-of-time, besides showing longer freezing time, which was not observed in animals exposed to HPME. Therefore, our study indicates the ecotoxicological potential of the herbicide, since anti-predatory behavior disorders may affect preys' responses and population dynamics.

Positive or negative emotion induced by feeding success or failure can affect behaviors, heart rate and immunity of suckling calves

This study investigated behavioral and physiological responses of suckling calves to either positive or negative situations. Twelve healthy female suckling Holstein calves at approximately 30 days of age were randomly selected and allocated to two groups: a) a positive situation (POS) group that received a feed reward and b) a negative situation (NEG) group that experienced food frustration. Behavior, heart rate (HR), and immune parameters were measured during the emotion-inducing periods and analyzed via ANOVA. The results indicated that the POS calves showed significantly increased locomotive play but decreased self-grooming, head shaking, and tongue-rolling behaviors as compared to the NEG counterparts (p < .05). The NEG calves had the highest HR (p < .01) after negative emotion induction. Salivary cortisol (S-CORT) level significantly increased following both positive and negative emotional induction (p < .05). In humoral immunity, serum concentrations of IgA were not significantly affected by either the positive or negative situation (p > .05), but the salivary SIgA level of the POS calves was higher than that of the NEG group (p < .01). Serum IL-2 and IL-3 levels in the POS calves were significantly higher than those of the NEG group (p < .01). However, the serum TNF-α level in the POS group was significantly lower than in the NEG group (p < .05). The results suggest that hunger satiation or food frustration may induce different behavioral and physiological responses in suckling calves, presenting an interesting set of reactions appropriate in response to the emotional situations elicited by this short-term stimulus

Reducing Astrocyte Calcium Signaling In Vivo Alters Striatal Microcircuits and Causes Repetitive Behavior

Astrocytes tile the central nervous system, but their functions in neural microcircuits invivo and their roles in mammalian behavior remain incompletely defined. We used two-photon laser scanning microscopy, electrophysiology, MINIscopes, RNA-seq, and a genetic approach to explore the effects of reduced striatal astrocyte Ca2+ signaling invivo. In wild-type mice, reducing striatal astrocyte Ca2+-dependent signaling increased repetitive self-grooming behaviors by altering medium spiny neuron (MSN) activity. The mechanism involved astrocyte-mediated neuromodulation facilitated by ambient GABA and was corrected by blocking astrocyte GABA transporter 3 (GAT-3). Furthermore, in a mouse model of Huntington's disease, dysregulation of GABA and astrocyte Ca2+ signaling accompanied excessive self-grooming, which was relieved by blocking GAT-3. Assessments with RNA-seq revealed astrocyte genes and pathways regulated by Ca2+ signaling in a cell-autonomous and non-cell-autonomous manner, including Rab11a, a regulator of GAT-3 functional expression. Thus, striatal astrocytes contribute to neuromodulation controlling mouse obsessive-compulsive-like behavior.

Long-Term Stress and Concomitant Marijuana Smoke Exposure Affect Physiology, Behavior and Adult Hippocampal Neurogenesis

Marijuana is a widely used recreational drug with increasing legalization worldwide for medical purposes. Most experimental studies use either synthetic or plant-derived cannabinoids to investigate the effect of cannabinoids on anxiety and cognitive functions. The aim of this study was to mimic real life situations where young people smoke cannabis regularly to relax from everyday stress. Therefore, we exposed young adult male NMRI mice to daily stress and concomitant marijuana smoke for 2 months and investigated the consequences on physiology, behavior and adult hippocampal neurogenesis. Animals were restrained for 6-h/day for 5-days a week. During the stress, mice were exposed to cannabis smoke for 2 × 30 min/day. We burned 2 “joints” (2 × 0.8 g marijuana) per occasion in a whole body smoking chamber. Cannabinoid content of the smoke and urine samples was measured by HPLC and SFC-MS/MS. Body weight gain was recorded daily and we did unrestrained, whole body plethysmography to investigate pulmonary functions. The cognitive performance of the animals was evaluated by the novel object recognition and Y maze tests. Anxietyrelated spontaneous locomotor activity and self-grooming were assessed in the open field test (OFT). Adult neurogenesis was quantified post mortem in the hippocampal dentate gyrus. The proliferative activity of the precursor cells was detected by the use of the exogenous marker 5-bromo-20-deoxyuridine. Treatment effects on maturing neurons were studied by the examination of doublecortin-positive neurons. Both stress and cannabis exposure significantly reduced body weight gain. Cannabis smoke had no effect on pulmonary functions, but stress delayed the maturation of several lung functions. Neither stress, nor cannabis smoke affected the cognitive functioning of the animals. Results of the OFT revealed that cannabis had a mild anxiolytic effect and markedly increased self-grooming behavior. Stress blocked cell proliferation in the dentate gyrus, but cannabis had no effect on this parameter. Marijuana smoke however had a pronounced impact on doublecortin-positive neurons influencing their number, morphology and migration. In summary, we report here that long-term stress in combination with cannabis smoke exposure can alter several health-related measures, but the present experimental design could not reveal any interaction between these two treatment factors except for body weight gain.

Effects of combined pre- and post-natal enrichment on anxiety-like, social, and cognitive behaviours in juvenile and adult rat offspring

The pre- and post-natal periods are characterized by unrivalled growth and are sensitive to environmental changes. A correctly stimulating early environment is essential for developing natural behaviors and maintaining affective wellness. Five litters of rat progeny were co-housed through gestation until juvenile age in housing providing physical and social enrichment. Five control litters were housed separately in standard conditions. Half of the offspring were tested in the elevated plus-maze and the social interaction test as juveniles (five weeks old) with the other half tested in the Morris water maze. As adults (11 weeks old), the testing groups were reversed. Weight was monitored weekly. Enriched offspring had leaner body weights. In the elevated plus-maze, control juvenile progeny spent a higher percentage of time in the open arms, showed greater locomotor activity, less grooming, and more rearing (males only). In the social interaction test, enriched juvenile offspring were found to sniff their conspecific more, display more self-grooming behaviour as well as show less locomotor activity and body contact. In the Morris water maze probe test, enriched rats demonstrated improved memory for the platform position and more effective search strategies with increased platform crossings, middle crossing as well as more time spent in the platform quadrant and less thigmotaxis behaviour. Adult female rat offspring also demonstrated superior memory for the platform position and crossed the maze middle more often. These results suggest that combined pre- and post-natal environmental enrichment influences physiology and behaviour in offspring rats with some of those influences being long-lasting.

Autism-specific maternal autoantibodies produce behavioral abnormalities in an endogenous antigen-driven mouse model of autism

Immune dysregulation has been noted consistently in individuals with autism spectrum disorder (ASD) and their families, including the presence of autoantibodies reactive to fetal brain proteins in nearly a quarter of mothers of children with ASD versus less than 1% in mothers of typically developing children. Our lab recently identified the peptide epitope sequences on seven antigenic proteins targeted by these maternal autoantibodies. Through immunization with these peptide epitopes, we have successfully created an endogenous, antigen-driven mouse model that ensures a constant exposure to the salient autoantibodies throughout gestation in C57BL/6J mice. This exposure more naturally mimics what is observed in mothers of children with ASD. Male and female offspring were tested using a comprehensive sequence of behavioral assays as well as measures of health and development highly relevant to ASD. We found that MAR-ASD male and female offspring had significant alterations in development and social interactions during dyadic play. Although 3-chambered social approach was not significantly different, fewer social interactions with an estrous female were noted in the adult male MAR-ASD animals, as well as reduced vocalizations emitted in response to social cues with robust repetitive self-grooming behaviors relative to saline treated controls. The generation of MAR ASD-specific epitope autoantibodies in female mice prior to breeding created a model that demonstrates for the first time that ASD-specific antigen-induced maternal autoantibodies produced alterations in a constellation of ASD-relevant behaviors.

Certain behavioral characteristics and stress responses of out-of-breeding ewes and rams during an intensive fattening program

The aim was to investigate behaviors and stress responses of rams and ewes in an intensive fattening period. Out-of-breeding rams (Hemsin = 10, Karakul = 10) and ewes (Hemsin = 8, Karakul = 10) were used in the study. Sheep and rams belonging to each breed were placed into four different pens. Behavioral observations (individual, feeding, abnormal self-grooming behaviors) were performed 2 days a week for two groups a day for 1 h. Blood samples were collected at the beginning, at the 4th week, and at the end of the fattening period. Karakul ewes displayed significantly more feeding and rumination behavior than Hemsin ewes, while there was no significant difference between ram groups. Ewes displayed more lying and rumination behavior than rams in the current study. On the other hand, rams were more active than ewes and also showed more abnormal behavior (butting other animals) during the fattening period. Sheep breed had no influence on packed cell volume (PCV), hemoglobin (Hb) concentration, or cortisol level at any sampling time. PCV, Hb, and cortisol levels at the middle of the fattening period were higher in ewes than rams. In conclusion, the behavioral repertoire of Hemsin and Karakul breeds in intensive fattening does not reveal any stress responses.