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PubMedDate not supplied

A chick model for the mechanisms of mustard gas neurobehavioral teratogenicity.

The chemical warfare blistering agent, sulfur mustard (SM), is a powerful mutagen and carcinogen. Due to its similarity to the related chemotherapy agents nitrogen mustard (mechlorethamine), it is expected to act as a developmental neurotoxicant. The present study was designed to establish a chick model for the mechanisms of SM on neurobehavioral teratogenicity, free of confounds related to mammalian maternal effects. Chicken eggs were injected with SM at a dose range of 0.0017-17.0 microg/kg of egg, which is below the threshold for dysmorphology, on incubation days (ID) 2 and 7, and then tests were conducted posthatching. Exposure to SM elicited significant deficits in the intermedial part of the hyperstriatum ventrale (IMHV)-related imprinting behavior. Parallel decreases were found in the level of membrane PKCgamma in the IMHV, while eliciting no net change in cytosolic PKCgamma. The chick, thus, provides a suitable model for the rapid evaluation of SM behavioral teratogenicity and elucidation of the mechanisms underlying behavioral anomalies. The results obtained, using a model that controls for confounding maternal effects, may be replicated in the mammalian model and provide the groundwork for studies designed to offset or reverse the SM-induced neurobehavioral defects in both avian and mammals.

Analysis of Variance↗
PubMed2001

Low-threshold N-methyl-D-aspartate receptor function correlates negatively with learning.

The intermediate, medial hyperstriatum ventrale (IMHV) is an area of the forebrain of the domestic chick which exhibits great plasticity. Moreover, there is a strong link between plasticity in the IMHV and specific changes in behaviour. The IMHV in vitro is still plastic, and many of its physiological properties are age-dependent, peaking in slices taken from 3- or 4-day-old birds. This 'window' coincides with an important transitional period in a chick's normal behavioural development. It has also been claimed that reversal training is at its most effective in 3- and 4-day-old birds - a proposition which was confirmed by the experiments reported here. A combination of in vivo training followed by in vitro electrophysiology also revealed that the function of low-threshold N-methyl-D-aspartate receptors (one of the age-related variables) is negatively related to the effectiveness of reversal training, when age is held constant.

Age Factors↗
PubMed2002

Androgen imprinting of the brain in animal models and humans with intersex disorders: review and recommendations.

PURPOSE: Psychosexual development, gender assignment and surgical treatment in patients with intersex are controversial issues in the medical literature. Some groups are of the opinion that gender identity and sexual orientation are determined prenatally secondary to the fetal hormonal environment causing irreversible development of the nervous system. We reviewed the evidence in animal and human studies to determine the possible role of early postnatal androgen production in gender development. MATERIALS AND METHODS: An extensive literature review was performed of data from animal experiments and human studies. RESULTS Many animal studies show that adding or removing hormonal stimulus in early postnatal life can profoundly alter gender behavior of the adult animal. Human case studies show that late intervention is unable to reverse gender orientation from male to female. Most studies have not permitted testing of whether early gender assignment and treatment as female with suppression/ablation of postnatal androgen production leads to improved concordance of the gender identity and sex of rearing. CONCLUSIONS: Animal studies support a role for postnatal androgens in brain/behavior development with human studies neither completely supportive nor antagonistic. Therefore, gender assignment in infants with intersex should be made with the possibility in mind that postnatal testicular hormones at ages 1 to 6 months may affect gender identity. A case-control study is required to test the hypothesis that postnatal androgen exposure may convert ambisexual brain functions to committed male behavior patterns.

Androgens↗
PubMed2003

Effect of neonatal beta-endorphin imprinting on sexual behavior and brain serotonin level in adult rats.

A single dose (3 microg) beta-endorphin was administered to newborn female and male rats (hormonal imprinting). In adult age (at 5 months) sexual behavior, steroid hormone binding capacity and brain serotonin content was studied. Females' sexual activity (lordosis quotient) significantly decreased and more animals protested against mounting (ratio of kicking and crying 21/24 vs. 8/24; p < 0.001). Males' sexual activity did not change, however more males were aggressive (4/10 vs. 1/10). Uterine estrogen receptor density significantly increased and affinity decreased. There was no change in the binding capacity of thymic glucocorticoid receptors. In the brain, five regions were studied for serotonin content. There was a gender difference in serotonin level and the intragroup differences were also high. In the endorphin treated males the serotonin level was significantly lower than in the controls. In the endorphin treated females the intragroup scattering has been significantly reduced. Nociceptin content of the cerebrospinal fluid was not changed. The experiments call attention to the possibility of adjustment of sexual and behavioral sphere by the individually different endorphin surge during labor.

Aggression↗
PubMed2003

Variations in maternal care in the rat as a mediating influence for the effects of environment on development.

Variations in maternal care have been widely considered as a critical influence in development. In the rat, variations in maternal behavior, particularly in licking/grooming, regulate the development of endocrine, emotional and cognitive responses to stress. These studies form the basis of a potentially useful model for the study of maternal effects in mammals. In this paper we provide a detailed methodological investigation into this model of maternal behavior, providing an analysis of the frequency, temporal dynamics, and transmission of maternal licking/grooming in several large cohorts. Frequency data indicate that licking/grooming is normally distributed across dams. The peak in licking/grooming occurs in the first few days postpartum and gradually declines. Dams designated as High or Low LG mothers differ in this behavior only during the first week postpartum. Observations over Days 2 to 5 postpartum are essential for the reliable assessments of individual differences in maternal behavior. Individual differences in licking/grooming behavior are stable across multiple litters, and are not associated with differences in litter size, weaning weight of pups, or gender ratio of the litter. We also observed no significant differences in the amount of licking/grooming received by individual pups within a litter, though variation does exist. Finally, maternal licking/grooming is transmitted to female offspring, though there is considerable within-litter variation in the expression of this behavior. Overall, these findings indicate considerable, normal variations in licking/grooming in the rat that are a stable, individual characteristic of rat dams.

Adaptation, Physiological↗
PubMed1997

Delayed induction of a filial predisposition in the chick after anaesthesia.

In domestic chicks, Gallus gallus domesticus, early filial preferences are formed as the result of at least two processes: learning by exposure to conspicuous objects (filial imprinting) and a developing predisposition to approach some stimuli rather than others. The predisposition may be measured in visually naive chicks, e.g. as a preference for a rotating stuffed jungle fowl hen rather than for a rotating red box. Non-specific experience, such as handling or being placed in a running wheel in darkness, for a short time, is sufficient to induce the predisposition. In Experiment 1, the existence of a sensitive period for the induction of the predisposition, between approximately 14 and 42 h after hatching, was confirmed. The putative effect of anaesthesia on the induction of the predisposition was investigated in Experiment 2. Soon after hatching dark-reared chicks received injections of the anaesthetic equithesin (0.12 ml, I.P.), or saline, or they did not receive injections (controls). The chicks were subsequently placed in running wheels for a total of 2 h at either 24 h or 48 h after hatching. The following day the chicks' preferences were tested. In the 24 h-chicks, the saline and control groups showed a significant mean preference for the stuffed fowl, whilst the equithesin group did not. In contrast, in the 48 h-groups of chicks, only the equithesin group showed a significant mean preference for the stuffed fowl. These results suggest that the anaesthetic equithesin affects a developing filial predisposition in the domestic chick, and does so by delaying the onset of a sensitive period for the induction of the predisposition.

Anesthesia↗
PubMed1997

Pharmacological extension of the sensitive period for imprinting in Gallus domesticus.

Precocial animals, such as the chick, exhibit a form of learning termed filial imprinting. The chick's sensitive period for filial imprinting is restricted to the first few days after hatching. The neural mechanism that terminates the sensitive period is not fully understood. It is thought to be an experience-dependent event because once a chick has imprinted, it will not readily imprint on another stimulus. However, even dark-reared chicks eventually lose the ability to imprint, which suggests that the ending of the sensitive period may not be entirely experience-dependent. The present study investigates factors that may contribute to the ending of the sensitive period. In our experiments, dark-reared chicks were unable to imprint after Day 2 posthatching, but chicks treated 10 h after hatching with an intramuscular injection of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine (55 mg/kg) and the alpha2-adrenoceptor agonist xylazine (6 mg/kg) (KX) imprinted on a stuffed hen 8 days after hatching. Similarly treated chicks did not imprint on a red and black box, although the box was an effective imprinting stimulus for Day 2 chicks. Chicks treated with KX at 20 or 40 h posthatching or on Day 4 or 7 as well as controls treated with pyrogen-free saline were unable to imprint on Day 8.

Adrenergic alpha-Agonists↗
PubMed2000

NMDA receptor antagonists extend the sensitive period for imprinting.

Filial imprinting in the domestic chick occurs during a sensitive period of development. The exact timing of this period can vary according to the methods used to measure imprinting. Using our imprinting paradigm, we have shown that normal, dark-reared chicks lose the ability to imprint after the second day post-hatching. Further, we reported that chicks treated 10 h after hatching with a mixture of the noncompetitive NMDA receptor antagonist ketamine (55 mg/kg) and the alpha(2)-adrenergic receptor agonist xylazine (6 mg/kg) were able to imprint on day 8 after hatching, whereas controls treated with saline did not imprint. We now show that the effect of the ketamine-xylazine mixture can be mimicked by treating chicks with ketamine alone or with another noncompetitive NMDA receptor antagonist, MK-801 (5 mg/kg). Treating chicks with a single dose of ketamine (55 mg/kg) or with a single dose of xylazine (6 mg/kg) failed to produce the effect on the sensitive period. However, prolonging the action of ketamine by treating chicks with two doses of ketamine (at 10 and 12 h after hatching) did allow imprinting on day 8. In contrast, prolonging the action of xylazine had no effect on the sensitive period for imprinting. Chicks treated with MK-801 were also able to imprint on day 8. Thus, we have evidence that the NMDA receptor system is involved in the mechanisms that control the sensitive period for imprinting.

Adrenergic alpha-Agonists↗