Responses In Behavioral Tests Research Articles

Galanin(1-15) Potentiates the Antidepressant-like Effects Induced by Escitalopram in a Rat Model of Depression.

Selective 5-HT reuptake inhibitor antidepressants (SSRIs) are the first choice in major depressive disorder (MDD), but 50% of affected patients do not show improvement. Galanin(1-15) [GAL(1-15)] enhanced Fluoxetine antidepressant-like effects in an animal model of depression, the olfactory bulbectomy (OBX); however, further detailed analysis of GAL(1-15) effects as augmentation treatment in OBX rats are needed. In OBX rats, we analysed the effect of GAL(1–15) on Escitalopram (ESC)-mediated responses in behavioural tests related to despair. We studied whether GAL(1–15) effects involved 5-HT1AR using an in vivo model siRNA 5-HT1A knockdown rats. Moreover, we analysed by immunohistochemistry the expression of the immediate-early gene c-Fos (c-Fos IR) after the administration of GAL(1-15)+ESC in OBX rats in several nuclei involved in MDD. GAL(1-15) enhances the antidepressant-like effects of ESC, and the GALR2 antagonist M871 blocked GAL(1-15) mediated actions. The downregulation of 5-HT1AR by siRNA was sufficient to block GAL(1-15) effects. Our immunohistochemistry and principal component analysis (PCA) analysis suggest that two functional networks are involved in these effects; one includes the lateral (LHb) and medial (mHb) habenula, dorsal raphe (DR) and ventral tegmental area (VTA), and the other consists of the dentate gyrus (DG), and prefrontal cortex (PFC). The results open up the possibility of using GAL(1-15) in combination with SSRIs as a novel strategy for treating MDD.

Nicotine aversion is mediated by GABAergic interpeduncular nucleus inputs to laterodorsal tegmentum

Nicotine use can lead to dependence through complex processes that are regulated by both its rewarding and aversive effects. Recent studies show that aversive nicotine doses activate excitatory inputs to the interpeduncular nucleus (IPN) from the medial habenula (MHb), but the downstream targets of the IPN that mediate aversion are unknown. Here we show that IPN projections to the laterodorsal tegmentum (LDTg) are GABAergic using optogenetics in tissue slices from mouse brain. Selective stimulation of these IPN axon terminals in LDTg in vivo elicits avoidance behavior, suggesting that these projections contribute to aversion. Nicotine modulates these synapses in a concentration-dependent manner, with strong enhancement only seen at higher concentrations that elicit aversive responses in behavioral tests. Optogenetic inhibition of the IPN–LDTg connection blocks nicotine conditioned place aversion, suggesting that the IPN–LDTg connection is a critical part of the circuitry that mediates the aversive effects of nicotine.

Longitudinal FDG microPET imaging of neuropathic pain: does cerebellar activity correlate with neuropathic pain development in a rat model?

We used [F-18] FDG microPET imaging as part of a longitudinal study to investigate changes in the brain. Glucose metabolism during the development of neuropathic pain after tibial and sural nerve transection (TST) model rats. MicroPET images were obtained 1 week before operation and then weekly for 8 weeks post-operation. The behavioral test was performed immediately after the every FDG administration. After TST modeling, neuropathic pain rats showed increased mechanical sensitivity of the injured hind paw. The withdrawal response to mechanical pain stimulation by von Frey filaments was observed within the first week (3.8 ± 0.73), and it rapidly increased in the third week (7.13 ± 0.82). This response reached a peak in the fourth week after surgery (9.0 ± 0.53), which persisted until the eighth week. In microPET scan imaging, cerebellum, which initially started from the ansiform lobule, was activated gradually to all part from the third week in all image acquisitions through the eighth week. The longitudinal microPET scan study of brains from neuropathic pain rat models showed sequential cerebellar activity that was in accordance with results from behavioral test responses, thus supporting a role for the cerebellum in the development of neuropathic pain.

Critical Role of GFRα1 in the Development and Function of the Main Olfactory System

Glial cell line-derived neurotrophic factor (GDNF) and its receptor GFRα1 are prominently expressed in the olfactory epithelium (OE) and olfactory bulb (OB), but their importance for olfactory system development is completely unknown. We have investigated the consequences of GFRα1 deficiency for mouse olfactory system development and function. In the OE, GFRα1 was expressed in basal precursors, immature olfactory sensory neurons (OSNs), and olfactory ensheathing cells (OECs), but was excluded from mature OSNs. The OE of newborn Gfra1 knock-out mice was thinner and contained fewer OSNs, but more dividing precursors, suggesting deficient neurogenesis. Immature OSN axon bundles were enlarged and associated OECs increased, indicating impaired migration of OECs and OSN axons. In the OB, GFRα1 was expressed in immature OSN axons and OECs of the nerve layer, as well as mitral and tufted cells, but was excluded from GABAergic interneurons. In newborn knock-outs, the nerve layer was dramatically reduced, exhibiting fewer axons and OECs. Bulbs were smaller and presented fewer and disorganized glomeruli and a significant reduction in mitral cells. Numbers of tyrosine hydroxylase-, calbindin-, and calretinin-expressing interneurons were also reduced in newborn mice lacking Gfra1. At birth, the OE and OB of Gdnf knock-out mice displayed comparable phenotypes. Similar deficits were also found in adult heterozygous Gfra1(+/-) mutants, which in addition displayed diminished responses in behavioral tests of olfactory function. We conclude that GFRα1 is critical for the development and function of the main olfactory system, contributing to the development and allocation of all major classes of neurons and glial cells.

Hearing Evaluation for Pediatric Cochlear Implant with ASSR

Objective: The aim of this study was to evaluate Auditory Steady-State Responses (ASSR) at high intensities in pediatric cochlear implant candidates and to compare the results to behavioral test responses. Method: This prospective study evaluated 54 children with severe-to-profound hearing loss, aged from 3 to 72 months, between January and December 2011. All had absent ABR and OAE responses. ASSR were evoked using binaural single frequency stimuli at 110 dBHL with a 10 dB-down seeking procedure. ASSR and behavioral test results were compared. Results: Forty-two subjects completed both ASSR and behavioral evaluation. In 13 children behavioral tests were not available, 1 had inconclusive ASSR. Among 42 children with absent ABR and OAE, 11 (26.1%) had bilateral ASSR, 10 correlated well to behavioral results. Four (9.5%) showed unilateral responses in at least 2 frequencies, all confirmed by behavioral results. Among 27 subjects with absent ASSR, 8 had no behavioral responses; 12 had responses only in low frequencies >110 dBHL, 7 showed behavioral responses at all frequencies in medium to high intensities. No spurious ASSR responses were observed at 100 or 110 dBHL in any frequency. Conclusion: ASSR is a valuable tool to detect residual hearing in young children with absent ABR and OAE. No false-positive ASSR results were observed, but in 7 cases with absent ASSR, the test underestimated residual hearing as compared to the behavioral responses.

Comparison of the kappa-opioid receptor antagonist DIPPA in tests of anxiety-like behavior between Wistar Kyoto and Sprague Dawley rats

Recent evidence suggests a role for the dynorphin/kappa-opioid receptor (KOR) system in the expression of stress-induced behaviors. Wistar Kyoto (WKY) rats exhibit increased depression-like and anxiety-like responses in behavioral tests compared to other strains and may be a model of comorbid depression and anxiety characterized by increased activity within the dynorphin/KOR system. Though KOR antagonists produce antidepressant-like effects in WKY rats, their effects in tests of anxiety-like behavior have not been examined in the WKY strain. The aim of the current study was to investigate the effects of the KOR antagonist 2-(3,4-dichlorophenyl)-N-methyl-N-[(1S)-1-(3-isothiocyanatophenyl)-2-(1-pyrrolidinyl)ethyl]acetamide hydrochloride (DIPPA) on the behavior of WKY rats and Sprague Dawley (SD) rats in tests of anxiety-like behavior. The novelty-induced hypophagia and defensive burying tests were used to measure anxiety-like behavior in WKY and SD rats and determine the effects of DIPPA on anxiety-like behavior in both strains. WKY rats displayed greater amounts of anxiety-like behavior compared to SD rats. DIPPA produced anxiolytic-like effects in both tests in both strains. WKY rats display more anxiety-like behavior at baseline compared to SD rats, and DIPPA produced anxiolytic-like effects in both WKY and SD rats. These findings support previous research suggesting that KOR antagonists possess anxiolytic-like properties and may potentially represent a novel class of treatments for mood disorders.

Methylmercury Pause: Study Suggests Long Latency for Neurotoxicity

Vol. 116, No. 6 EnvironewsOpen AccessMethylmercury Pause: Study Suggests Long Latency for Neurotoxicity Julia R. Barrett Julia R. Barrett Search for more papers by this author Published:1 June 2008https://doi.org/10.1289/ehp.116-a259aAboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit Methylmercury (MeHg) easily crosses the blood–brain barrier and accumulates in the central nervous system, where it is demethylated to inorganic mercury. Chronic perinatal exposure to environmentally relevant levels of MeHg is associated with the occurrence later in childhood of neurobehavioral problems such as impaired attention and fine motor function. Animal studies confirm this association, but epidemiologic evidence is mixed despite extensive study. Moreover, MeHg toxicity and the period of time before effects appear are not completely understood, as few studies have been conducted beyond the first months or years of life in either animals or humans. Researchers now demonstrate in a mouse model that effects from early exposure to methylmercury can occur years after early-life mercury levels in the brain have declined [EHP 116:746–751; Yoshida et al.].In the current study, investigators used two strains of mice—the wild-type C57BL strain and the genetically manipulated metallothionein (MT)-null strain. The latter was used to examine potential genetic susceptibility to the toxic effects of MeHg exposure, as MT-null mice do not produce metallothionein-I and II proteins that can bind metals and protect against their toxic effects. Mice were exposed through diet to low levels of MeHg (5 μg/g diet) from the first day of pregnancy through the tenth day after birth. Offspring of the treated mice were weaned at 28 days. At 12 and 52 weeks (roughly comparable to young adulthood and middle age in humans), the offspring underwent behavioral tests of their locomotor activity and learning ability. All animals were weighed biweekly, and mercury concentrations in the brains, livers, and kidneys were measured for 10-day-old mice and for the group tested at 12 weeks.In 10-day-old exposed mice, mercury concentrations in the brain were 0.5 μg Hg/g body weight or lower, with no significant differences observed between exposed wild-type mice and MT-null mice. At 13 weeks, concentrations of mercury in the brain of exposed groups were similar to those of the unexposed groups. Except for one activity measure in female MT-null mice, exposure to MeHg did not significantly affect behavioral test responses at 12 weeks. At 52 weeks, however, investigators observed significant effects in all behavioral test responses, with MT-null mice being slightly more affected. After 28 weeks, wild-type male and all MT-null mice exposed to MeHg weighed significantly less than control mice, which may signal an emerging toxic effect.The authors demonstrate a long latency period after perinatal exposure to low levels of MeHg and show that this period may be influenced by genetic susceptibility, given the stronger effect of MeHg exposure in MT-null mice. The existence of a latency period suggests that a slow process, such as aging, plays a role in MeHg toxicity, although the actual damage occurs much earlier in life.FiguresReferencesRelatedDetails Vol. 116, No. 6 June 2008Metrics About Article Metrics Publication History Originally published1 June 2008Published in print1 June 2008 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

Corticotrophin releasing factor-induced synaptic plasticity in the amygdala translates stress into emotional disorders.

The amygdala is involved in the associative processes for both appetitive and aversive emotions, and its function is modulated by stress hormones. The neuropeptide corticotrophin releasing factor (CRF) is released during stress and has been linked to many stress-related behavioral, autonomic, and endocrine responses. In the present study, nonanxiety-inducing doses of a potent CRF type 1 and 2 receptor agonist, urocortin (Ucn), was infused locally into the basolateral amygdala (BLA) of rats. After 5 daily injections of Ucn, the animals developed anxiety-like responses in behavioral tests. Intravenous administration of the anxiogenic agent sodium lactate elicited robust increases in blood pressure, respiratory rate, and heart rate. Furthermore, in the absence of any additional Ucn treatment, these behavioral and autonomic responses persisted for >30 d. Whole-cell patch-clamp recordings from BLA neurons of these hyper-reactive animals revealed a pronounced reduction in both spontaneous and stimulation-evoked IPSPs, leading to a hyperexcitability of the BLA network. This Ucn-induced plasticity appears to be dependent on NMDA receptor and subsequent calcium-calmodulin-dependent protein kinase II (CaMKII) activation, because it is blocked by pretreatment with NMDA receptor antagonists and by coadministration of CaMKII inhibitors. Our results show for the first time a stress peptide-induced behavioral syndrome that can be correlated with cellular mechanisms of neural plasticity, a novel mechanism that may explain the etiological role of stress in several chronic psychiatric and medical disorders.

Cuticular hydrocarbons of Heterotermes tenuis (Isoptera: Rhinotermitidae): analyses and electrophysiological studies.

Termites have become an important pest of Eucalyptus and Pinus reforestations, sugarcane and other cultures. An alternative for the control of this pest would be the use of attractive traps that take in account the social behavior of these insects. Diverse factors are important for the insects in the localization of the habitat and the choice of the food and specific odors can facilitate this. Studies referring to Heterotermes tenuis (Isoptera: Rhinotermitidae) are scarce. The objective of this work was to analyze the tergal cuticular extract of H. tenuis and determine the selectivity and sensitivity of its antennae to the components of this extract by electroantennography (EAG). The composition of the cuticular extract was determined by GC-MS analysis. The hydrocarbons found were restricted to linear alkanes, being most abundant C24 to C27 that comprises ca. 65% of the total. Olefins were not detected. EAG and behavioral test responses to the cuticular hydrocarbons were greater and significantly different from the control and the high selectivity of the antennae to the extract indicates its potential as chemical messenger. Cuticular hydrocarbons mixture is species-specific and can be used to identify a given taxon without the diagnostic castes, soldiers or imagoes Difference in the composition appears to relate with the type of habitat of specie.

Strain and age differences in behaviour, fear response and pecking tendency in laying hens

1. Behaviours associated with a high or low tendency to feather peck could be used as predictors of feather pecking behaviour in selective breeding programmes. This study investigated how strain and age at testing influenced responses in behavioural tests. 2. Four layer-type strains (ISA Brown, Columbian Blacktail, Ixworth and a high feather pecking (HP) and a low feather pecking (LP) line of White Leghorn) were reared in 6 same-strain/line pens of 8 birds from one day old. Birds in half the pens were given an open field test, a novel object test and a test with loose feather bundles between 4 and 12 weeks of age and a tonic immobility (TI) test at 13 weeks of age. All pens were tested with fixed feather bundles at 26 weeks, and undisturbed behaviour in the home pens was videoed at 1 and 27 weeks of age. Daily records of plumage damage were used as an indicator of feather pecking activity in the home pens. 3. Strain did not influence novel object test, open field test or loose feather test behaviour, although age effects in all three tests indicated a reduction in fearfulness and/or an increase in exploratory behaviour with increasing age. 4. White Leghorns showed longer TI durations than the other strains but less pecking at fixed feather bundles than ISA Browns and Columbian Blacktails. 5. There were few associations between behaviour in the 5 different tests, indicating that birds did not have overall behavioural traits that were consistent across different contexts. This suggests hens cannot easily be categorised into different behavioural 'types', based on their test responses and casts doubt on the usefulness of tests as predictors of feather pecking.

Responses of horses in behavioural tests correlate with temperament assessed by riders.

Behavioural tests as well as observers' ratings have been used to study horses' temperament. However, the relationship between the ratings and the responses in behavioural tests has not yet been studied in detail. The aim of the present study was to examine this relationship between ratings and responses. Eighteen mature Swedish Warmblood horses were subjected to 2 behavioural tests, one relating to novelty (novel object test) and one to handling (handling test). Subsequently, 16 of these horses were ridden by 16 equally experienced students, having no former experience with the horses. Immediately after each ride, the students scored the horse for 10 temperamental traits using a line rating method. It was shown that for each temperamental trait all 16 riders agreed on the ranking of the horses (0.212<W<0.505, P < 0.001). Correlations between behavioural and heart rate variables in the behavioural tests revealed that horses with a high level of locomotion or much restlessness behaviour exhibited high mean heart rate and low heart rate variability. In particular, heart rate variables in the behavioural tests were found to correlate with riders' rating scores. Furthermore, the underlying components of the handling test, retrieved with a principal component analysis (PCA) correlated with riders' rating scores while the underlying components of the novel object test did not. It is concluded that it is possible for a large panel of assessors to agree upon a horse's temperament and that objective measures from behavioural tests correlate significantly with temperamental traits assessed by a panel of assessors.

Sublethal poisoning: A comparison of behavior and histological changes in house fly CNS

House flies examined the day after receiving sublethal doses of lindane or carbofuran showed a statistically significant decline in their responses to behavioral tests designed to measure flight, locomotion, optomotor activity, and phototaxis. Flies were designated “functional,” “flightless,” or “nontestable” on the basis of their behavioral test responses. Histological examination of their thoracic ganglia revealed holes in the neuropile, termed “vacuoles,” but no “vacuoles” were evident in the ganglia of control flies. There was a statistically significant correlation between the density of “vacuoles” in the thoracic ganglia of lindane-treated flies and their phototactic responses and climbing performance. This correlation was not demonstrated for the carbofuran-treated group. They were less responsive to behavior tests than the lindane-treated group and had more “vacuoles” in their thoracic ganglia. Flight functions were evidently most susceptible to poisoning; some flies were “flightless” but appeared to have normal locomotor functions with few, if any, “vacuoles” evident in the ventral neuropile of their thoracic ganglia. “Vacuoles” were always present in the dorsal or central regions of the mesothoracic neuromeres of “flightless” flies. Flies with disabled legs always had “vacuoles” in the ventral neuropile or their ganglia. Heartbeat recorded the day after poisoning with lindane or carbofuran was usually irregular in amplitude and rate, suggesting that motor innervation from the central nervous system remained functional. Flight motor activity was depressed the day after poisoning in comparison to that recorded from untreated flies.