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PubMed2001

Neurobehavioral assessment of outcome following traumatic brain injury in rats: an evaluation of selected measures.

Neurobehavioral assessment of outcome has played an integral part in traumatic brain injury (TBI) research. Given the fundamental role of neurobehavioral measurement, it is critical that the tasks used are of the highest psychometric quality. The purpose of this paper is to evaluate several, commonly used neurobehavioral measures along the dimensions of reliability, sensitivity, and validity. Using both the midline and lateral fluid-percussion injury models, nine neurobehavioral measures were evaluated that assessed three different neurobehavioral constructs. Reflex suppression was measured by the duration of the suppression of the pinna, corneal, and righting reflexes. Vestibulomotor function was assessed with the beam-balance, beam-walking, and rotorod tasks. Cognitive function was evaluated by three measures of Morris water maze performance (goal latency, path length, cumulative distance). The evaluation of the reliability of the nine neurobehavioral measures found that all had acceptably high reliability coefficients (0.79 or higher). The analysis of each measure's sensitivity to injury found that all measures were capable of detecting injury-induced impairments. However, there were some substantial differences in the sensitivity of the measures of vestibulomotor and maze performance: the rotorod was the most sensitive vestibulomotor measure and goal latency and path length were equally sensitive measures of maze performance. In the assessment of validity, the results of a factor analysis supported the convergent and discriminative validity of the measures. And in cases in which the preclinical and clinical research have assessed the same construct, the animal model neurobehavioral measures had predictive (or external) validity. Thus, according to the psychometric standards by which measurement instruments are evaluated, the results indicated that these measures provide a valid assessment of neurobehavioral function after fluid percussion TBI.

Animals↗

PubMed1986

Behavior and viability of the premature neonatal foal after induced parturition.

Parturition was induced in 2 groups of mares, less than 300 (n = 49) and 300 to 320 days gestation (n = 31), by the administration of prostaglandin F2 alpha or fluprostenol and oxytocin. Foals were categorized into 4 groups according to their ability to adapt in, and survive, the neonatal period. Group A had no demonstrable coordinating reflexes, were weak from birth, and all died within 90 minutes. Group B had some righting reflexes, but had poor coordination and a weak suck reflex. They showed some improvement for about 2 hours, but all died within 9 hours. Group C foals had a good suck reflex and made attempts to stand. After 24 hours, there was a steady deterioration and death occurred within 48 hours. Group D were initially weak, but showed rapid clinical improvement with good adaptation to the environment and survived for at least 7 days. The overall survival rate for the 80 foals born was only 5%. Most group A foals had gestational ages of less than 300 days, but a few (n = 9) were delivered after 300 days and 2 up to 319 days. The youngest survivor was delivered at 318 days and the 3 other survivors were delivered at 320 days. Aspects of the hazards of prematurely induced parturition were considered to be immaturity and stress of parturition.

Animals↗

PubMed1991

The inverse relationship between nonverbal intelligence and the latency of the Hoffmann reflex from the right and left thenar muscles in right- and left-handed subjects.

The relationship between nonverbal reasoning ability and the latency of the Hoffmann (H) reflex was studied in right- and left-handed subjects. The nonverbal reasoning ability was assessed by the Cattell's Culture Fair Intelligence test. Hand preference was assessed by the Edinburgh Handedness Inventory. Hoffmann reflex was recorded from thenar muscles of the right and left thumbs. In left-handers (total sample), IQ was found to be significantly and negatively linearly related to the H-reflex latency from the left side. In strong left-handers, there was a significant negative linear relationship between IQ and the H-reflex latency from right and left sides, but with a higher correlation for the left side. In weak left-handers, IQ did not show any significant relation to the H-reflex latencies from the right and left sides. In right-handers (total sample), there was a significant negative linear correlation between IQ and the H-reflex latency from the right side. In right-handed women without familial sinistrality (FS-), IQ was found to be inversely related to the H-reflex latency from the right and left side, but with a higher correlation for the right side. In right-handed women with FS, IQ did not show any significant relation to the H-reflex latency from the right and left sides. In right-handed men with right eye preference and FS-, IQ was found to be negatively linearly related to the H-reflex latency from the right and left sides equally. In right-handed men with right eye FS+, mixed eye FS-, +, mixed eye-right foot (FS-), mixed eye-mixed foot, and left eye preference there was no significant relationship between IQ and the H-reflex latency from the right and left sides. Only in strong left-handers there was a significant, positive linear correlation between IQ and the right minus left (R-L) difference of latencies. The H-reflex latency from the right and left sides was not significantly correlated with the R-L difference of latencies in left-handers. In right-handed women with right eye preference FS-, and in right-handed men with right eye preferences FS-, The H-reflex latency from the right side was found to be positively linearly correlated with the R-L difference of latencies. In right-handed women FS+, and in right-handed men FS+, and mixed or left eye preference, the H-reflex latency from the left side was found to be negatively linearly related to the R-L difference of latencies.(ABSTRACT TRUNCATED AT 400 WORDS)

Female↗

PubMed1985

Effect of electroconvulsive shock on the somatosensory evoked potential in the rat.

The effect of electroconvulsive shock (ECS) on the cortical somatosensory evoked potential (SEP) was studied in 25 male rats. SEPs were recorded after stimulation of the contralateral forepaw. Animals were curarized and artificially ventilated but not anesthetized. The magnitude of the ECS was 80 mA for 600 ms which produced tonic-clonic convulsions lasting an average 54 s in noncurarized control animals. SEPs were recorded during the ictal period and then at intervals for 20 min. ECS initially caused the total abolition of all components of the SEP implying a significant but transient effect on activity propagated in specific and also possibly diffuse somatosensory pathways. The reappearance of the SEP coincided with the cessation of convulsive movements and the return of the corneal reflex. The return of the waveform to near baseline condition corresponded to the regaining of the righting reflex at approximately 3 min in the control animals. The most persisting change in the SEP waveform was in the shape of the late high-amplitude component (N2) which may reflect activity in the reticular formation. Following ECS, N2 reappeared with a peak latency notably decreased (approximately 1 ms) in comparison with the mean baseline recording. There was also an attenuation in the amplitude of N2 which remained significantly depressed (at less than 50% of mean baseline amplitude) throughout the post-ECS recording period. The results are compared with the relatively few studies of the acute effects of ECS on evoked potentials in psychiatric patients and also with a neuroendocrine theory which argues that the principal site and mode of action of ECS lies in the diencephalon.

Action Potentials↗

PubMed1994

Behavioral deficits following experimental subarachnoid hemorrhage in the rat.

To characterize some of the short-term and long-term functional consequences of subarachnoid hemorrhage (SAH) in rats, we employed a battery of well-characterized tests for assessment of acute and chronic behavioral and neurologic performances. Three groups of 10 rats (blood injected, mock CSF injected and sham-operated controls) were studied. During the acute stage, simple nonpostural somatomotor reflexes (pinna and corneal reflexes), simple postural responses (paw flexion, tail flexion, and head support), startle response, and postural functions (righting reflex) did not differ significantly between the experimental groups. Assessments of body weight, beam walking ability, and beam balancing revealed significant disturbances in blood-injected rats. This work demonstrates that this single-hemorrhage rodent model of SAH is associated with the induction of enduring neurologic and behavioral deficits. Because of the significant interspecies difference, a direct extrapolation of our results to humans may not be appropriate. However, we suggest that the observed behavioral and neurologic changes may parallel those seen in humans after SAH. Results reported here further confirm the rat model of SAH as a viable laboratory instrument for the study of the pathophysiology of SAH and provide normative values for the evaluation of new treatment modalities.

Acute Disease↗

PubMed2005

Development of neurological reflexes and motor coordination in rats neonatally treated with monosodium glutamate.

Monosodium glutamate (MSG) treatment of neonatal rats causes neuronal degeneration in various brain areas and leads to several neurochemical, endocrinological and behavioral alterations. However, relatively little is known about the development of neurological reflexes and motor coordination of these animals. Therefore, the aim of the present study was to examine the neurobehavioral development of newborn rats treated with MSG. Rats received MSG at postnatal days 1, 3, 5, 7, and 9. Appearance of neural reflexes and reflex performance as well as motor coordination were examined for 5 weeks after birth. The efficacy of MSG treatment was confirmed by histological examination of the arcuate nucleus. We found that MSG treatment delayed the appearance of forelimb placing, forelimb grasp and righting reflexes, besides the retarded somatic development. The treated pups performed surface righting in significantly longer times. Also, worse performance was observed in the foot-fault and rota-rod tests. However, MSG-treated rats reached control levels by the end of the fifth postnatal week. These results show that MSG treatment does not cause permanent alterations in the neurobehavioral development, only delays the appearance of some reflexes and leads to temporary changes in reflex performance and motor coordination signs.

Analysis of Variance↗

PubMed1989

Neonatal development altered by maternal sulfur dioxide exposure.

Sulfur dioxide (SO2) is one of the commonly encountered environmental contaminants. Experiments were carried out to test for neonatal behavioral alterations associated with maternal SO2 exposure. Pregnant CD-I mice were exposed to 0, 32, or 65 PPM SO2 in environmental chambers from gestation day 7 to 18 (plug = day 1). The SO2 air flow was set at 500 ml/min. Food and water were available at all times. The dams were allowed to deliver and neonatal behavioral development of the pups was studied. Maternal SO2 exposure did not affect the mean number of live pups born/litter; however, the exposure at the high level significantly decreased the mean pup weight on day 1 of birth. SO2 exposure at both levels significantly increased the time required for the righting reflex on day 1 of birth and negative geotaxis on day 10 of birth. The SO2 exposure did not affect the aerial righting score of the pups on day 12 of birth. The data suggest that maternal SO2 exposure can affect the neuromuscular coordination and may produce deficits in the functional capability of the developing offspring. The functional deficits appear to be associated with the birth weight of the offspring.

Animals↗

PubMed2004

Neurobehavioral effects in rat pups whose sires were exposed to alcohol.

Developmental neurobehavioral effects associated with maternal exposure to alcohol during pregnancy are well described, but little is known about the effects of paternal exposure prior to conception. Using a quasi-experimental, within-subjects design, neurobehavioral outcomes (reflex acquisition, activity, gait) and cerebral cortical layer thickness were assessed in Sprague-Dawley rat pups from breeding pairs where the sires were exposed to alcohol. Comparisons were made on the basis of the timing of conception relative to alcohol exposure: phase 1 (controls), prior to initiation of alcohol exposure; phase 2, during the period of treatment with 20% alcohol; and phase 3, following cessation of alcohol exposure. Phase 2 and 3 pups were noted to attain negative geotaxis and reflex suspension benchmarks earlier than control pups and to have more difficulty with balance. Phase 3 pups were noted to attain righting reflex earlier than controls. In addition, phase 3 pups demonstrated increased levels of reverse maze activity and a shorter and narrower gait. Brain morphometry revealed thickening of cortical sections I-IV and V-VI resulting in overall cortical enlargement in both phase 2 and 3 pups. Further analysis of phase 2 and 3 subphases based on the presumed stages of the spermatogenic cycle during which sires were exposed to alcohol revealed significant differences in maze activity, reflex acquisition, and gait length. These findings suggest pre-conception male exposure to alcohol may have an effect on the offspring and the extent of the effects may vary with the timing of alcohol exposure relative to conception.

Alcohol Drinking↗

PubMed1975

Developmental and behavioral changes in the rat during chronic exposure to lead.

Young male and female Sprague-Dawley rats were given drinking water containing 5 or 50 ppm Pb for 40 days prior to mating. Pregnant females were continued on these regimens throughout gestation and lactation. After weaning the offspring were similarly exposed through adulthood. Reflex development, body weights, and locomotor activity were measured in the offspring. Significant delays were noted in the development of the righting reflex at 5 and 50 ppm and in eye opening at 50 ppm. No difference was observed in development of the startle reflex at either dose. Mean body weights of treatment groups during this developmental period were not significantly different from controls. Locomotor activity was measured in adult males utilizing a residential maze. Both levels of lead produced a significant reduction in locomotor activity. When groups were treated with d-amphetamine (4.0 mg/kg subcutaneous), lead treatment caused a dose-related diminution in the amphetamine-induced hyperactivity. These results indicate that rats exposed to low levels of lead from conception until adulthood show a delay in nervous system development. As adults, these animals exhibit hypoactivity and decreased responsiveness to amphetamine.

Aging↗

PubMed1997

Responses to propofol in relation to GABA functionality of discrete parts of the brain of rats.

Genetically-determined regional differences in the GABA-ergic make-up of the brain exist in two lines of Wistar rats viz apomorphine-susceptible (APO-SUS) and apomorphine-unsusceptible (APO-UNSUS) Wistar rats, Propofol is a GABA-mimetic general anesthetic. This study compared the responses to propofol in APO-SUS and APO-UNSUS rats. Propofol induced a higher incidence of involuntary muscular contractions and oral movements, but a lower incidence of grooming, in APO-SUS rats than in APO-UNSUS rats. Reflex inhibition and narcosis, being defined as the behavior marked by both full absence of purposeful movements and by complete loss of righting reflexes, after propofol did not differ between the two lines. APO-SUS rats had less variation of the heart rates and greater variations of diastolic arterial pressures in response to electrical stimulation than the APO-UNSUS rats, and these variations were reduced by increasing doses of propofol. Arterial pressures in APO-SUS rats were higher than in APO-UNSUS rats. Propofol caused a biphasic change in intra-arterial pressures and had the greatest effect in APO-SUS rats. Differences in cerebral GABA transmission, especially in the striato-nigro-collicular pathway, did not give rise to differences in the effect of propofol on narcosis and hindlimb withdrawal reflex. In contrast, these differences in GABA transmission were accompanied by line-specific differences in effect of propofol on certain behavioral and cardiovascular parameters.

Anesthesia, Intravenous↗

PubMed1994

alpha-Difluoromethylornithine delays behavioral recovery and induces decompensation after unilateral labyrinthectomy.

Biochemical and pharmacologic studies suggest a role for the ornithine decarboxylase-polyamine system as a modulator of behavioral changes during vestibular compensation. alpha-Difluoromethylornithine specifically blocks the rate-limiting step of polyamine biosynthesis. To assess the effects of alpha-difluoromethylornithine on the acute phase of postural compensation, guinea pigs were divided into groups subjected to either unilateral labyrinthectomy only (n = 7), alpha-difluoromethylornithine (500 mg/kg/day) for 4 days before labyrinthectomy (n = 10), equivalent volumes of saline for 4 days before labyrinthectomy (n = 8), and sham operations (n = 5). Yaw head tilt and roll head tilt, trunk curvature, and air-righting reflex were measured at baseline and at regular intervals up to 4 weeks. alpha-Difluoromethylornithine significantly delayed recovery of normal air-righting but had no effect on yaw head tilt, roll head tilt, and trunk curvature. We also evaluated effects of alpha-difluoromethylornithine in compensated guinea pigs. Fully compensated animals from phase 1 were randomly assigned to receive alpha-difluoromethylornithine (500 mg/kg/day) or saline once daily for 4 days. Only 33% of alpha-difluoromethylornithine animals maintained air-righting, compared with 100% of saline-treated animals (p = 0.003). Maximum trunk curvature was greater in the alpha-difluoromethylornithine group (p = 0.02). Thus alpha-difluoromethylornithine not only delayed the time course for postural recovery after unilateral labyrinthectomy, it also transiently disrupted the maintenance of the compensated state.

Animals↗

PubMedDate not supplied

Behavioral alterations induced in rats by a pre- and postnatal exposure to 2,4-dichlorophenoxyacetic acid.

The purpose of this study was to determine whether the behavioral development pattern was altered by a pre- and postnatal exposure to 2,4-Dichlorophenoxyacetic acid (2,4-D). Pregnant rats were daily orally exposed to 70 mg/kg/day of 2,4-D from gestation day (GD) 16 to postnatal day (PND) 23. After weaning, the pups were assigned to one of the two subgroups: T1 (fed with untreated diet until PND 90) and T2 (maintained with 2,4-D diet until PND 90). Effects on offsprings were evaluated with a neurotoxicological test battery. Neuromotor reflexes, spontaneous motor activity, serotonin syndrome, circling, and catalepsy were analyzed during various postnatal ages. 2,4-D neonatal exposure induced delay of the ontogeny of righting reflex and negative geotaxis accompanied by motor abnormalities, stereotypic behaviors (excessive grooming and vertical head movements), and hyperactivity in the open field. Adult rats of both sexes (T2 group) showed a diminution of ambulation and rearing, while excessive grooming responses were only observed in T2 males. Besides, these animals manifested serotonin syndrome behaviors, catalepsy, and right-turning preference. Some behaviors were reversible, but others were permanent, and some were only expressed after pharmacological challenges.

2,4-Dichlorophenoxyacetic Acid↗

PubMedDate not supplied

Effects of bromantan on offspring maturation and development of reflexes.

Bromantan (N-[2-adamantil]-N-[para-bromphenyl]amine) is an "actoprotective" drug widely used in Russia as a muscle performance-enhancing agent for sportsmen and as an immunostimulator in medicine. Experiments were conducted to determine whether this compound has adverse effects on the reproduction and development of offspring. Sexually mature female rats, weighing 180-200 g, were orally given bromantan at doses of 30 mg/kg (30-mg/kg group), 150 mg/kg (150-mg/kg group) and 600 mg/kg (600-mg/kg group) daily for 16 days, while the controls received the vehicle, amylaceous solution. Afterwards, treated females were mated with untreated males. The body weight change of the pregnant rats was monitored, as well as the length of gestation, litter size, sex ratio and number of stillborn. The offsprings were weighed and observed for external malformations, abnormalities of conditioned and unconditioned reflexes and open-field behaviour. Observation of rat dams revealed that their general state and activity in all groups did not differ significantly both during and after bromantan treatment. Bromantan had no adverse effects on body weight and gestation length of dams. Number of dams delivered per group did not differ from controls. There were stillborn rat pups in all litters, but the control group had less. One dam in the first group delivered a rat pup with a head hematoma. Litter size of the 30- and 600-mg/kg groups was decreased (by 34.9% and 44.2%, respectively) and increased in the 150-mg/kg group (by 45.1%, P< .05) in comparison with controls. Bromantan had insignificant different effects on the sex ratio of newborn in all treatment groups. Survival of pups over the first 3 months showed a loss of 40% for the 150-mg/kg group and 20% for controls. During the remaining time, death rate did not exceed 3-6% and did not differ from those of the controls. Pups in the 30- and 600-mg/kg groups showed significantly higher weight gain during the first week (7th PND) of observation by 83.69% and 58.02%, respectively, compared to controls; subsequently, this difference in the 600-mg/kg group decreased rapidly to insignificant levels, but the 30-mg/kg group remained significantly different until PND 35 and then again at PND 77-112. Dynamics of body weight gain of rat pups in the 150-mg/kg group during the whole (but not on PND 7) period of observation was insignificantly (on PNDs 14, 42 and 49 significantly) lower than that of the control group. Study of the functional state of rat pups' nervous system at different stages of postnatal development revealed insignificant differences in the expression of reflexes compared with those of the control group. Negative geotaxis was completed by the 8th day in controls and in treated groups earlier by an average of 1-2 days. Surface righting was completed by the controls on the 8th day, in the 30-mg/kg group on the 6th day and in other treated groups on the 7th day. Cliff avoidance appeared a day ahead for rat pups in treated groups compared with controls. Air righting reflex in the 30- and 600-mg/kg groups was observed a day earlier than in the controls. Significant differences were observed only for two parameters (negative geotaxis and surface righting); in both cases, rat pups of the 30-mg/kg group differed from the control and 150-mg/kg groups. Early development of physical parameters was also noted, but significant differences from the control group were obtained only in the 30-mg/kg group for incisor eruption. While all pups demonstrated strength of fore and hind limbs by postnatal day 16, treated pups increased their times of maintaining their grasp (PND 15). Open-field testing (PND 40) resulted in an insignificant decrease of exploratory and locomotor behaviors for the 30-, 150- and 600-mg/kg groups. The number of grooming episodes was insignificantly decreased for the 30-mg/kg group and insignificantly increased for the 600-mg/kg group. In the passive avoidance testing, on the retention day (72 h later), entry latency for rat pups in the 30-, 150- and 600-mg/kg groups increased by 259.0%, 175.3% and 160.7%, respectively (P< .05), over their training day, while in the control group, time increased only by 1.8%.

Amantadine↗

PubMed2006

Paradoxical effects of prenatal acetylcholinesterase blockade on neuro-behavioral development and drug-induced stereotypies in reeler mutant mice.

INTRODUCTION: Epidemiological and experimental studies support a link between genetic and epigenetic factors in vulnerability to develop enduring neurobehavioral alterations. We studied the interplay between genetic vulnerability and the prenatal exposure to a neurotoxic compound. Chlorpyrifos, a potent and reversible acetylcholinesterase blocker used as a pesticide, and the "reeler" mouse, lacking the extracellular-matrix protein Reelin, were used. MATERIALS AND METHODS: Homozygous reeler (RL), heterozygous (HZ), and wild-type (WT) mice were prenatally exposed to chlorpyrifos-oxon (CPF-O), the active metabolite of chlorpyrifos, or to vehicle (prenatal controls) on gestation days 14-16, that is, during a peak period of neurogenesis in the cerebral cortex. The offspring was reared by the natural dam and tested during infancy and at adulthood for global consequences of the prenatal exposure. CONCLUSION: The results are consistent with complex interactions between genetic (reeler genotype) and epigenetic (prenatal exposure to CPF-O) factors. In the case of some "genetically modulated" parameters (ultrasound vocalization, amphetamine-induced locomotion, and stereotypy), exposure to CPF-O paradoxically reverted the effects produced by progressive reelin absence. Conversely, for an "epigenetically modulated" parameter (grasping reflex maturation), the effects of CPF-O exposure were counteracted by progressive reelin absence. Finally, for parameters apparently untouched by either factor alone (righting reflex latency, scopolamine-induced locomotor activity), prenatal CPF-O exposure unmasked an otherwise latent genotype dependency. This complex picture also points to reciprocal adaptations within cholinergic and dopaminergic systems during development. Data are interesting in view of recently discovered cholinergic abnormalities in autism and schizophrenia, and may suggest new avenues for early intervention.

Amphetamine↗

PubMed1999

Delayed development of reflexes and hyperactive locomotion in the spontaneous mutant "waltzing" of the musk shrew, Suncus murinus.

The autosomal recessive mutation waltzing (wz), displaying abnormal circling and head-shaking behavior, has previously been reported in the musk shrew (Suncus murinus). Postnatal development of reflexes and locomotor patterns in an open arena were examined in wz/wz mutant shrews. The wz/wz shrews showed extreme developmental delays in surface-righting reflex and negative geotaxis until 10-16 days after birth, but both reflexes eventually recovered to the levels of +/wz normal. Nevertheless, the wz/wz adults exhibited bi-directional circling behavior 59 times, head-tossing behavior 22 times and horizontal head-shaking behavior 6 times more frequent than in the +/wz controls. Although the wz/wz adult shrews were extremely hyperactive with daily spontaneous locomotor activity exceeding 4-7 times control shrew activity, they appeared to have a normal circadian rhythm. This shrew mutant may therefore be useful as a model for hyperactivity syndromes in humans.

Animals↗

PubMed1997

Developmental and behavioral effects of postnatal amitraz exposure in rats.

The effects of postnatal amitraz exposure on physical and behavioral parameters were studied in Wistar rats, whose lactating dams received the pesticide (10 mg/kg) orally on days 1, 4, 7, 10, 13, 16 and 19 of lactation; control dams received distilled water (1 ml/kg) on the same days. A total of 18 different litters (9 of them control and 9 experimental) born after a 21-day gestation were used. The results showed that the median effective time (ET50) for fur development, eye opening, testis descent and onset of the startle response were increased in rats postnatally exposed to amitraz (2.7, 15.1, 21.6 and 15.3 days, respectively) compared to those of the control pups (1.8, 14.0, 19.9 and 12.9 days, respectively). The ages of incisor eruption, total unfolding of the external ears, vaginal and ear opening and the time taken to perform the grasping hindlimb reflex were not affected by amitraz exposure. Pups from dams treated with amitraz during lactation took more time (in seconds) to perform the surface righting reflex on postnatal days (PND) 3 (25.0 +/- 2.0), 4 (12.3 +/- 1.2) and 5 (8.7 +/- 0.9) in relation to controls (10.6 +/- 1.2; 4.5 +/- 0.6 and 3.4 +/- 0.4, respectively); the climbing response was not changed by amitraz. Postnatal amitraz exposure increased spontaneous motor activity of male and female pups in the open-field on PND 16 (140 +/- 11) and 17 (124 +/- 12), and 16 (104 +/- 9), 17 (137 +/- 9) and 18 (106 +/- 8), respectively. Data on spontaneous motor activity of the control male and female pups were 59 +/- 11 and 69 +/- 10 for days 16 and 17 and 49 +/- 9, 48 +/- 7 and 56 +/- 7 for days 16, 17 and 18, respectively. Some qualitative differences were also observed in spontaneous motor behavior; thus, raising the head, shoulder and pelvis matured one or two days later in the amitraz-treated offspring. Postnatal amitraz exposure did not change locomotion and rearing frequencies or immobility time in the open-field on PND 30, 60 and 90. The present findings indicate that postnatal exposure to amitraz caused transient developmental and behavioral changes in the exposed offspring and suggest that further investigation of the potential health risk of amitraz exposure to developing human and animal offsprings may be warranted.

Animals↗

PubMed1999

Behavioral phenotyping of transgenic and knockout mice: experimental design and evaluation of general health, sensory functions, motor abilities, and specific behavioral tests.

Rigorous experimental design can minimize the high risk of false positives and false negatives in the behavioral phenotyping of a new transgenic or knockout mouse. Use of well established, quantitative, reproducible behavioral tasks, appropriate Ns, correct statistical methods, consideration of background genes contributed by the parental strains, and attention to litter and gender issues, will maximize meaningful comparisons of -/-, +/-, and +/+ genotypes. Strategies developed and used by our laboratory are described in this review. Preliminary observations evaluate general health and neurological reflexes. Sensory abilities and motor functions are extensively quantitated. Specific tests include observations of home cage behaviors, body weight, body temperature, appearance of the fur and whiskers, righting reflex, acoustic startle, eye blink, pupil constriction, vibrissae reflex, pinna reflex, Digiscan open field locomotion, rotarod motor coordination, hanging wire, footprint pathway, visual cliff, auditory threshold, pain threshold, and olfactory acuity. Hypothesis testing then focuses on at least three well-validated tasks within each relevant behavioral domain. Specific tests for mice are described herein for the domains of learning and memory, feeding, nociception, and behaviors relevant to discrete symptoms of human anxiety, depression, schizophrenia, and drug addiction. An example of our approach is illustrated in the behavioral phenotyping of C/EBPdelta knockout mice, which appear to be normal on general health, neurological reflexes, sensory and motor tasks, and the Morris water task, but show remarkably enhanced performance on contextual fear conditioning.

Animals↗

PubMed1985

Antagonistic effects of S9871 or (imidazolinyl-2)-2-dihydro 2,3 benzofurane and its stereoisomers on some central and peripheral actions of alpha 2-agonists.

(+/-) and (+), but not (-) S9871 are new alpha 2-adrenoceptor selective antagonists. The effect of the racemic mixture and of the stereoisomers on cardiovascular and sedative responses to clonidine have been studied in rats and chickens, respectively. Blockade of central alpha 2-adrenoceptors was also measured as a recovery of the sympathoinhibitory effect induced by intravenous administration of B-HT 933 (azepexole). The potency profiles of these agents established in the central nervous system were confirmed in studies using the vas deferens in situ in the pithed rat. (+/-) and (+) S9871 blocked and antagonized some centrally mediated effects of clonidine such as the depressor response to both intravenous and intracerebroventricular administration. However, the return of arterial pressure to the control value, after intravenous administration of (-) S9871, does not result from an antagonistic action on alpha 2-adrenoceptors, since the depressor effects of clonidine were not blocked, but could be explained by alpha-agonistic properties of (-) S9871. (+/-) and (+) S9871 also blocked and antagonized the hypotensive and bradycardic action induced by intravenous administration of B-HT 933. The loss of the righting reflex induced by clonidine in the chicken was prevented by (+/-) and (+) S9871, as shown by a shift of the dose-response curve to clonidine to the right by both agents; on the contrary, (-) S9871 potentiated the sedation induced by clonidine. In the pithed rat, intravenously administered (+/-) and (+) S9871 fully antagonized the inhibitory effects of clonidine on the electrically induced contractions of the vas deferens. These observations are consistent with a selective alpha 2-adrenoceptors antagonistic effect of (+/-) and (+) S9871 at central and peripheral alpha 2-adrenoceptors.

Adrenergic alpha-Agonists↗