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PubMedDate not supplied

Neurobehavioral toxicology of halothane in rats.

Halothane, a commonly used general anesthetic, is considered to be relatively safe for that purpose. Chronic exposure, however, has been found to cause long-lasting damage to neural structure and impairment of behavioral function. In rats, behavioral alterations are particularly evident after developmental exposure, but they can also be seen with adult exposure, especially when halothane is given during the period of neural regrowth following a brain lesion. The pattern of neural damage includes retarded synaptogenesis, impaired dendritic branching and disruption of organelle structure. The behavioral syndrome includes learning impairment, decreased exploratory behavior and decreased nociceptive reactivity. In general, the neural pathology is more pronounced and more easily discernible than the behavioral effects. Neural damage, particularly to the hippocampus, can be clearly seen at points when behavioral impairments have not been found. This demonstrates that in some cases changes in neural structure can be more sensitive indicators of toxic damage than behavioral dysfunction. Halothane exposure has proved to be quite useful as an experimental tool in the study of neural and behavioral recovery after brain lesions. For example, after unilateral entorhinal cortical lesions, behavioral recovery and reactive synaptogenesis occur contemporaneously. It has not been demonstrated whether the behavioral recovery is due to this reinnervation. Postlesion halothane exposure almost completely suppresses reactive synaptogenesis, however, behavioral recovery of T-maze alternation behavior occurs in the halothane-treated rats as well as in controls. This suggests that recovery of spatial performance after such a lesion is not due to recovery of innervation in the dentate, but to some other process such as other neural systems taking over the functions lost with the brain lesion. The studies reviewed highlight the dangers of halothane exposure, especially during development or when recovering from brain injury. They also provide a good case study for comparing the relative sensitivity of morphological and behavioral measures in toxicology and point to the potential use of halothane as an experimental tool for examining the relationships between neural structure and behavioral function.

Animals↗
PubMed2006

HSP70 expression in the hippocampal CA3 subfield in different chronic stress models.

This study examined the heat shock protein 70 (HSP70) expression in hippocampal CA3 subfield of rats in different chronic stress models. The chronic restraint stress (CRS) and the chronic mild stress (CMS) models were used in this study. Observation of exploratory behavior in an open field test indicated stress level. The expression of HSP70 in hippocampal CA3 subfield was measured by immunohistochemical methods. The results showed that the number of quadrant crossing in both CRS and CMS groups decreased more than that of the control (P < 0.01). CRS group crossing decreased more than CMS group. Damage in the hippocampus of the CMS group occurred later and to a less extent than that of the CRS group. Compared with CMS group, the expression of HSP70 was greater in the CRS group. Moreover, increased stress duration enhanced these effects. These results show that the CRS model affects both exploratory behavior and HSP70 expression in the hippocampus more dramatically than the CMS model.

Animals↗
PubMed1990

Contrasting effects of centromedial and basolateral amygdaloid lesions on stress-related responses in the rat.

The effects of lesions in the centromedial and basolateral amygdala were examined using three different tests sensitive to the following stress-related responses: exploratory behavior, pain reactivity, and immune responses. The most clear-cut results were found with exploratory behavior. Rats with lesions of the centromedial amygdala tended to explore a radial-arm maze more quickly and entered more novel arms of the maze than controls. Those with lesions of the basolateral amygdala were generally too hesitant to explore at all. No significant differences were found between groups on measurements of natural killer cell activity. In tests of pain perception, rats in the control group displayed an analgesic response on the hot plate following an injection of the anxiogenic drug, RO 15-1788, whereas rats with centromedial lesions tended to exhibit a blunted response. These findings provide modest support for the view that the central and lateral regions of the amygdala play complementary roles in aversively motivated behaviors and in stress-related response patterns.

Amygdala↗
PubMed2001

Prenatal exposure to ethinylestradiol elicits behavioral abnormalities in the rat.

Pregnant rats were i.p. injected with a solution of 17alpha-ethinylestradiol (15 microg kg(-1)) every day between day 9 and day 14 of pregnancy and the behavior of the offspring was compared to that of rats born from dams injected with the vehicle only during the same gestational period. The percentage of neonatal death was dramatically high in the prenatally treated group. Growth of the surviving animals was even better than that of controls, but when adult, they exhibited a number of behavioral abnormalities: increased spontaneous motor activity, decreased exploratory behavior, impaired cognitive processing, qualitatively different exploratory drive, and/or persevering behavior, increased anxiety-like behavior and social neophobia. These behavioral alterations, which resemble a number of psychiatric syndromes, suggest that ethinylestradiol altered the ontogenesis of different parts of the central nervous system involved in cognitive and emotional processes. However, it cannot be excluded that the changes in behavior of ethinylestradiol exposed offspring were due to the abnormal maternal behavior of the estradiol treated dams.

Animals↗
PubMed2000

Age effects on the social interaction test in early adulthood male rats.

The effects of age on active and passive social interaction were studied in Wistar rats using the social interaction test (S.I.T.). Individual behaviors such as ambulation, rearing, and defecation were also studied. Despite the widespread use of the S.I.T. in anxiety research, the effects of age on the S.I.T. have not been studied thoroughly. Male Wistar rats of 75, 135, and 180 days old were used. Our results showed age effects on active social contact, passive social contact, ambulation, rearing, and defecation. At 135 days old, animals presented the lowest scores on active social behavior and the highest scores on defecation. Moreover, exploratory behavior measured by ambulation and rearing decreased with age. These results suggest that age could be a relevant variable in the social interaction test.

Aging↗
PubMed2003

Pharmacological activity of the essential oil of Satureja viminea (Lamiaceae).

The aqueous extract and the essential oil of Satureja viminea (Lamiaceae) were tested. General physiologic effects were assessed through the Hippocratic screening test. Non fasted female Sprague Dawley rats were utilized and 250, 500, 750 and 1000 mg/kg doses were used. Two animals were used for each dosage level and for the vehicle alone. Exploratory behavior and curiosity were measured using a hole board apparatus and placing non-trained mice on the board and recording the number of holes explored in a 5 minute period. The Boissier chimney test was used to evaluate motor coordination. Muscle strength was assessed through a grasping test where mice were hung by their fore-limbs 40 cm above the base on a horizontal metal stainless bar. In all these tests, 3 groups of 6 albino mice, were treated with 1000 mg/kg of each the essential oil of S. viminea, the vehicle and diazepan (1 mg/kg) as a positive control. Analgesic activity was explored in Sprague-Dawley rats. The tail flick method described by D'Amour and Smith (1941) modified by CYTED was implemented on three groups (6 rats each) of animals treated with, each the essential oil of S. viminea (1000 mg/kg), the vehicle and indomethacine. The test was carried out just before and 30, 60 and 120 min after oral treatment. Peristaltic activity was measured in albino mice, three groups of 6 animals each, treated orally with each the essential oil of S. viminea (1000 mg/kg), the aqueous extract (1000 mg/kg), and the vehicle. The marker used was activated carbon. Animals were sacrificed 30 min after the marker was given and the percent of total small intestine traversed by it was calculated. Also a lethal dose 50 (LD 50) was determined with the Spearman-Karber method. A dose-related spontaneous motor activity reduction was observed. Exploratory behavior and curiosity were diminished. The grasping strength of mice was reduced. A very clear and significant analgesic effect was observed with the oral administration of the essential oil of S. viminea (1000 mg/kg). This effect is compared to that of indomethacine. Intestinal transit and gastric emptying were inhibited by the essential oil. The LD50 of the essential oil of S. viminea is 556.8 mg/kg.

Analgesics↗
PubMed2000

The Peculiarities of the Immune Status in Mice with Different Level of Behavioral Reactions.

Within the framework of the problem of neuroimmune interrelationships we studied the peculiarities of the immune status in mice with different level of behavioral reactions. The parameters of humoral and cellular immunity, immunohaematological values and thymus weight in mice were investigated. Using the "open field" we estimated the exploratory behavior, general locomotor activity and emotional state in mice. It was found that (CBA x C57Bl/6)F1 mice may be divided into 3 following groups: with high, medium and low level according to a degree of pronounced signs of behavioral reactions. C57Bl/6 and Balb/c mice appeared to be opposite towards manifestation of studied behavioral reactions. All mice showed direct dependence between the initial level of exploratory behavior, general locomotor activity and pronounced signs of delayed type hypersensitivity as well as indirect dependence of this immunological parameter on the degree of emotional state. Thus, it can be concluded that there is a close link between functional activity of nervous system and expression of cellular immunity. The influence of immune system on the formation of the initial behavioral status in mice is supposed.

Journal Article↗
PubMed1986

Maternal separation alters later consumption of novel liquids in the squirrel monkey.

The consumption of novel, fruit-flavored drinks was measured in juvenile squirrel monkeys that had either had their mother removed from the home cage for 2 h on 80 occasions prior to weaning or had not undergone this separation procedure. Among previously separated animals, males drank more than did females during the first 30 min following presentation, whereas there was no difference in the drinking of nonseparated males and females at this time. Further, the amount of liquid consumed during the 20 h following presentation increased across days of exposure in the nonseparated, but not in the previously separated monkeys. These results show that brief maternal separation can affect the later behavior of squirrel monkeys, and are consistent with findings in rhesus macaques that maternal separation alters later exploratory behavior.

Animals↗
PubMed1977

The differential impact of self-monitoring on smoking behavior: an exploratory study.

This study investigated the impact of self-monitoring on smoking patterns of internal and external smokers. Eighty-nine Ss charted their smoking behavior (number of cigarettes per day) on a daily basis for 4 consecutive weeks, after which personality measures were administered. Self-monitoring produced wide changes in reported cigarette consumption, although this procedure did not change significantly smoking behavior for the entire sample. Ss were divided arbitrarily into three categories: Ss who increased 20 cigarettes or more, Ss who decreased 20 cigarettes or more, and Ss who increased or decreased up to 19 cigarettes. Negative affect traits, locus of control, and self-concept variables did not differentiate increasers, decreasers, or maintainers. Ss who increased consumption reported greater reinforcement value from solitary related as opposed to socially oriented functions than the decreasers and the maintainers. Future studies should explore the meaningfulness of an intervention designed to improve the smoker's social interactions.

Adult↗
PubMed1975

Compartive behavioral effects of dibutyryl cyclic AMP and prostaglandin E1 in mice.

Three behavioral tests, spontaneous locomotor activity (SLMA), exploratory behavior (EB) and rotarod performance (RP), a measure of neuromuscular coordination, were used to stuey the interaction of PGE1 (1 mg/kg i.p., 10 min. pretreatment) with DBcAMP (25 mg/kg i.p., 25 min. pretreatment) in mice. A dose-response relationship of PGE1 (0.01-5.0 mg/kg) to SLMA was determined, with a significant decrease in SLMA produced by a dose of 0.1 mg/kg. decreases in SLMA were produced by PGE1 (79%), DBcAMP (41%) and DBcAMP-PGE1 combination (71%). Similar decreases in EB were observed. Although no significant difference between controls and DBcAMP was observed in RP, 52% of mice tested were RP failures following PGE1 and a 100% failure rate was induced by the combination. Mice were treated with a second injection of DBcAMP or PGE1 or the combination 24 hr following the first injection. Behavioral activity of these mice was observed 25 min (DBcAMP) or 10 min (PGE1) after the second dose was administered. A second injection of DBcAMP failed to decrease SLMA and EB from controls; moreover, SLMA began to return towards control levels as early as 2 hr between injections. The second injection of PGE1 or DBcAMP+PGE1 produced the same behavior as that produced by the first injection. On the basis of these results, the relationship of cyclic nucleotides and PGs to behavioral activity is discussed.

Animals↗
PubMed1984

Tyrosine prevents behavioral and neurochemical correlates of an acute stress in rats.

Exposure of rats to an acute, uncontrollable stressor can increase brain norepinephrine (NE) turnover and decrease locomotor and exploratory behavior. We examined the ability of exogenous tyrosine, NE's amino acid precursor, to protect rats from developing these neurochemical and behavioral changes when stressed. Animals pretreated with saline or tyrosine (200 mg/kg, i.p.) were subjected to tail shock (15 v, 2 mA, 5 sec/30 sec) or to no shock during a 60-min period. Exposure to shock depleted NE and increased its turnover [as indicated by altered NE and 3-methoxy-4-hydroxy-phenylene-glycol sulfate levels (MHPG-SO4)] within the locus coeruleus, the hippocampus and the hypothalamus. Behavioral deficits were observed using measures of locomotion, standing on hind legs, and hole-poking in an open-field apparatus. Animals given tyrosine before shock displayed neither shock-induced NE depletion nor the deficits in locomotion and hole-poking; brain MHPG-SO4 levels tended to be greater than after shock alone. These observations suggest that the stress caused NE to be released from some neurons more rapidly than it could be restored by synthesis or reuptake, thereby impairing noradrenergic transmission and NE-dependent exploratory behaviors. Tyrosine administration presumably enhanced the transmitter's synthesis in stressed animals, thereby preventing both the neurochemical and the behavioral deficits.

Animals↗
PubMed2004

Alpha-tocopherol attenuates lipopolysaccharide-induced sickness behavior in mice.

Antioxidants protect cells from oxidative damage and reduce lipopolysaccharide (LPS)-induced expression of inflammatory cytokines. Because inflammatory cytokines induce sickness behavior, we hypothesized that antioxidants, namely alpha-tocopherol (alpha-T) and selenium would inhibit sickness behavior caused by LPS. In an initial study, mice were injected intraperitoneal (i.p.) with vehicle, 2, or 20mg alpha-T for 3 consecutive days and then challenged with vehicle, 1, 10, or 100 microg of LPS. Sickness behavior was quantified by measuring social exploratory behavior. Vehicle pretreated mice injected with LPS showed a marked reduction in social behavior at 4h (p < .01). However, sickness behavior induced by the lowest dose of LPS was partially or completely blocked by 2 or 20mg alpha-T, respectively. alpha-T did not prevent sickness from higher doses of LPS. In a second study, mice were fed AIN93-M modified diets containing 10, 75, and 500 mg alpha-T/kg and 0.05, 0.15, and 2mg selenium/kg for 8 weeks and then challenged with saline or LPS (1 microg). The highest concentration of dietary alpha-T and selenium tended (p = .1) to reduce LPS-induced sickness behavior. Mice fed diets low in antioxidants had reduced plasma alpha-T levels and glutathione peroxidase activity (p = .08 and p < .01, respectively) and elevated liver thiobarbituric acid reactive substances (p < .001) 24h post LPS. Collectively, these data indicate that alpha-T improved the oxidative status after exposure to LPS, which may explain its ability to ameliorate symptoms of sickness.

Analysis of Variance↗
PubMed2002

Relations between self-generated positive and negative expected smoking outcomes and smoking behavior: an exploratory study among adolescents.

The expected outcomes of drug use figure prominently in models of drug motivation. This report presents the relations between self-generated expected outcomes of smoking and smoking behavior in 674 adolescents. Expected outcomes of smoking were related to current smoking, experimentation, and susceptibility among never-smokers, even after controlling for key correlates of smoking behavior, including gender, grade, ethnicity, and peer smoking. Although more negative than positive smoking outcomes were accessible from memory, more positive than negative expected outcomes were correlated with smoking behavior. Both the content and number of self-generated expected outcomes provided unique associative information. In sum, greater elaboration of smoking-related memory networks, as well as the specific content of those networks, appear to be associated with smoking behavior.

Adolescent↗
PubMed2004

Prenatal exposure to methylphenidate hydrochloride decreases anxiety and increases exploration in mice.

The administration of methylphenidate (MPH) to girls and adults has increased in the last decade. Given the similarity of MPH to cocaine and the increasing possibility of embryonic exposure, the gestational effects of this stimulant on development must be considered. We administered MPH (5 mg/kg) or saline to female CD-1 mice at three different periods during pregnancy [embryonic (E) days 8-10, 12-14, and 16-18]. MPH-exposed pups were compared with the saline-treated pups for changes in physical, motor, and behavioral development at postnatal day (PND) 3-11. In adulthood (>60 days of age) these mice were tested in the open field, elevated plus maze, and water maze, and given an acute MPH challenge. We observed limited effects of MPH exposure on early developmental variables. In adulthood, mice exposed to MPH on E8-10 exhibited a general decrease in anxiety-related behaviors and a concomitant increase in exploratory behavior. Prenatal MPH exposure did not alter water maze performance or the response to an acute MPH challenge. Our data provide an initial overview of the possible effects occurring as a result of prenatal exposure to MPH, and strongly suggest that further studies of the in utero and developmental effects of psychostimulants are needed.

Animals↗
PubMed1990

Catecholamines and the initiation of sexual behavior in male rats without sexual experience.

The purpose of the present experiments was to investigate the effects of modified catecholaminergic neurotransmission upon sexual behavior in inexperienced males. Such males are critically dependent on stimuli from the female in order to initiate sexual behavior, and catecholamines are known to modulate interactions with environmental stimuli. It was found that D-amphetamine, 0.5 and 1 mg/kg, and amfonelic acid, 0.25 and 0.5 mg/kg, reduced mount and intromission latencies. Pimozide, in doses between 0.25 and 1 mg/kg, and cis(Z)-flupentixol, 0.5 mg/kg, reduced the proportion of animals displaying sexual behavior. The noradrenergic neurotoxin DSP4 (50 mg/kg one week before behavioral observation) shortened intromission latency while the noradrenaline precursor threo-dihydroxyphenylserine (10 mg/kg + carbidopa 50 mg/kg) increased mount and intromission latencies. In a test for social and exploratory behaviors it was found that amfonelic acid, in a dose of 0.5 mg/kg, augmented sniffing and rearing without affecting nonsexual interaction with a receptive female. Flupentixol (0.5 mg/kg) had a slight inhibitory effect on exploratory behavior and no effect on nonsexual interaction with a female. It is suggested that enhanced dopaminergic activity facilitates the initiation of sexual behavior due to an increased general arousal and not because of a specific effect on that behavior. The role of noradrenaline is less clear at present.

Animals↗
PubMed1999

Anxiety and increased 5-HT1A receptor response in NCAM null mutant mice.

Mice deficient in the neural cell adhesion molecule (NCAM) show behavioral abnormalities as adults, including altered exploratory behavior, deficits in spatial learning, and increased intermale aggression. Here, we report increased anxiety-like behavior of homozygous (NCAM-/-) and heterozygous (NCAM/-) mutant mice in a light/dark avoidance test, independent of genetic background and gender. Anxiety-like behavior was reduced in both NCAM+/+ and NCAM-/- mice by systemic administration of the benzodiazepine agonist diazepam and the 5-HT1A receptor agonists buspirone and 8-OH-DPAT. However, NCAM-/- mice showed anxiolytic-like effects at lower doses of buspirone and 8-OH-DPAT than NCAM+/+ mice. Such increased response to 5-HT1A receptor stimulation suggests a functional change in the serotonergic system of NCAM-/- mice, likely involved in the control of anxiety and aggression. However, 5-HT1A receptor binding and tissue content of serotonin and its metabolite 5-hydroxyindolacetic acid were found unaltered in every brain area of NCAM-/- mice investigated, indicating that expression of 5-HT1A receptors as well as synthesis and release of serotonin are largely unchanged in NCAM-/- mice. We hypothesize a critical involvement of endogenous NCAM in serotonergic transmission via 5-HT1A receptors and inwardly rectifying K+ channels as the respective effector systems.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2006

Head-cocking as a form of exploration in the common marmoset and its development.

Head-cocking of 15 infant marmosets (Callithrix jacchus) was scored from Day 1 to 60 of postnatal life, the growth period with overproduction of interneuronal synapses. Head-cocking was scored during four 30 min intervals daily, including angle of head-cocking and objects being fixated. Mean age of onset of head-cocking was Day 13 (+/-1.3) and frequency increased to a fixed rate by Day 24-29, at the time of maturation of the foveal representation in layer 6 of the visual cortex, thus lending further support to the importance of head-cocking to visual processing. The most common distance of objects fixated during head-cocking was up to .5 m. Angle of head-cocking increased with age, and some asymmetry of direction was noted. Fewer head-cocking events occurred in the morning than in the afternoon. We also scored anogenital licking of offspring. Head-cocking occurred at higher levels in marmosets receiving more anogenital licking. As this was associated positively with increased exploration, head-cocking may be regarded as an exploratory behavior.

Age Factors↗