Radioactive marking in the study of locomotion in small mammals.

A technique is described for continuous recording of locomotor activity in small mammals. A radioactive source (Ag 110^m), enclosed in a drop of resin, is fixed to the animal's cranium. The experimental chamber is a Plexiglas cylinder in the center of which is a radiation detector, whose electrical signals are integrated and recorded on moving paper. Each displacement of the animal gives rise to a variation in the intensity of radiation and thus to a variation in recording amplitude. Locomotor activity is quantified by counting the number of significant displacements in unit time. The technique is sufficiently sensitive to bring out the differences in locomotor activity between two strains of mice. In the rat, the effects of tryptophan deprivation on locomotor activity and time spent feeding have been studied. The applicability of this method is very wide, because it allows the measurement of movement of any animal in air, water, or on dry land. It is at the moment even being applied to the study of the vertical migration of plankton.     

Behavioral perturbations in the vitamin K-deficient rat

Anecdotal observations of the behavior of rats with a vitamin K-deficiency suggested that this deficiency was associated with hypoactivity, general malaise, and a lack of exploratory behavior. These observations were pursued by assessing locomotor activity in a circular photocell-monitored track, open-field activity, and radial-arm maze performance in rats rendered vitamin K-deficient by dietary depletion or by warfarin treatment. There was a significant reduction (approximately 25% at the median) in the locomotor activity of dietary vitamin K-deficient rats compared with rats fed a control diet. In the open-field, warfarin administration was associated with a significant shift from more exploratory behaviors to less exploratory behaviors. Consistent with these findings, radial-arm maze assessment showed a comparative reduction in locomotor activity in the dietary vitamin K-deficient rats with no alteration in performance, i.e., short-term memory. These animal behavioral studies suggest that sub-clinical and clinical vitamin K-deficiency may contribute to physical and psychiatric symptomatology.     

Repeated cocaine administration increases B-cell leukemia/lymphoma 2 phosphorylation in the rat dorsal striatum

Protein phosphorylation caused by drug administration is a critical step in the regulation of behavioral alterations. This study was conducted to determine how repeated exposure to cocaine phosphorylates B-cell leukemia/lymphoma 2 (Bcl2), which may be responsible for the regulation of behavioral alterations in the rat dorsal striatum. The results revealed that repeated systemic injections of cocaine (20 mg/kg) once a day for 7 consecutive days increased the phosphorylation of Bcl2 at serine 70 (Bcl2-S70). However, this increase was reduced by the blockade of dopamine D1 receptors, group I metabotropic glutamate receptors (mGluRs), and N-methyl-d-aspartate (NMDA) receptors. In addition, elevation of behavioral locomotor activity after repeated exposure to cocaine was partially reduced by the inhibition of Bcl2. These data suggest that stimulation of dopamine D1 receptors, group I mGluRs, and NMDA receptors following repeated cocaine administration is necessary for the induction of Bcl2-S70 phosphorylation, which contributes to the expression of behavioral sensitization.     

Strain differences and laminar localization of structural neurochemical changes in aging rat

To obtain comparisons of age-related microchemical changes in cerebral cortex of two comonly employed rat strains (Fischer 344 and Sprague-Dawley), neurochemical assays of substances regarded as quantitative indices of structural entities in brain were performed. These included DNA as a marker for cells, lipid sialoganglioside as an index of neuronal membrane mass, and galactocerebroside as an index of myelin. Fischer 344 rats were studied at 3–4 months (young), 14–16 months (middle age) and 25–28 months (old). Sprague-Dawleys were examined at 3–6 months (young), 14–17 months (middle age) and 25–28 months (old). Significant differences in the time courses of changes occurred; Fischer rats increased their brain weight at each aging point, while Sprague-Dawley rats reached stable brain weights by 4 months of age. Neither strain had a significant change in cell packing density of somatosensory cortex as measured by DNA. However, total ganglioside sialic acid declined in both strains, occurring by middle age in the Fischer and not until senescence in the Sprague-Dawley cortex. Cerebroside galactose increased in the Fischer between young and middle age, and was not further elevated in the older group. The Sprague-Dawley had its major increase in this marker between the middle aged and senescent groups. Intralaminar assays of these same markers in young and old Fisher 344 rats again indicated that DNA did not change, and that sialoganglioside was lost from all layers of the cortex in equal amounts. However, the increase in galactocerebroside resulted entirely from increases in the lower lamina of somatosensory cortex (lamina IV and below), suggesting on-going myelination of afferent and efferent axons. The time course of lipid membrane alteration is strain-dependent and selective as to cortical laminar localization. The findings are discussed in reference to human aging change in the same neurochemical indices.     

Strain differences and laminar localization of structural neurochemical changes in aging rat

To obtain comparisons of age-related microchemical changes in cerebral cortex of two comonly employed rat strains (Fischer 344 and Sprague-Dawley), neurochemical assays of substances regarded as quantitative indices of structural entities in brain were performed. These included DNA as a marker for cells, lipid sialoganglioside as an index of neuronal membrane mass, and galactocerebroside as an index of myelin. Fischer 344 rats were studied at 3–4 months (young), 14–16 months (middle age) and 25–28 months (old). Sprague-Dawleys were examined at 3–6 months (young), 14–17 months (middle age) and 25–28 months (old). Significant differences in the time courses of changes occurred; Fischer rats increased their brain weight at each aging point, while Sprague-Dawley rats reached stable brain weights by 4 months of age. Neither strain had a significant change in cell packing density of somatosensory cortex as measured by DNA. However, total ganglioside sialic acid declined in both strains, occurring by middle age in the Fischer and not until senescence in the Sprague-Dawley cortex. Cerebroside galactose increased in the Fischer between young and middle age, and was not further elevated in the older group. The Sprague-Dawley had its major increase in this marker between the middle aged and senescent groups. Intralaminar assays of these same markers in young and old Fisher 344 rats again indicated that DNA did not change, and that sialoganglioside was lost from all layers of the cortex in equal amounts. However, the increase in galactocerebroside resulted entirely from increases in the lower lamina of somatosensory cortex (lamina IV and below), suggesting on-going myelination of afferent and efferent axons. The time course of lipid membrane alteration is strain-dependent and selective as to cortical laminar localization. The findings are discussed in reference to human aging change in the same neurochemical indices.     

The behavioral change of locomotor activity in a kaolin-induced hydrocephalus rat model: Evaluation of the effect on the dopaminergic system with progressive ventricle dilatation

Hydrocephalus is a pathological enlargement of the cerebral ventricle that results from an obstruction of the space containing cerebrospinal fluid (CSF) in the brain. Motor abnormalities, such as abnormal gait and posture, are frequently seen in patients with hydrocephalus. The present study was designed to investigate locomotor activity in the elevated plus maze behaviorally. Hydrocephalus was induced in Sprague–Dawley rats by injection of 0.1 ml of 20% kaolin solution into the cisterna magna (n = 14). Control rats received the same volume of saline (n = 12). The rats were sacrificed at 3 days and 4 weeks after the elevated plus maze test. Tyrosine hydroxlyase (TH) immunoreactivity in the substantia nigra was evaluated by immunohistological staining. Hydrocephalic rats showed decreased motor activity for entries of arms when compared to control rats (p < 0.05). Compared to control rats, the number of TH immunoreactive neurons was significantly decreased in hydrocephalic rats. These results suggest that decreased motor responses due to ventricle enlargement in hydrocephalic rats are associated with the functional impairment of the central dopamine system.     

An analysis of neurophysiological and behavioral arousal in the mouse

Inbred mice of the C57BL/6 and DBA/2 strain differed for their spontaneous locomotor activity (Animex), reactivity (somatosensory orientation) and excitability (EEG desynchronization elicited by tactile stimuli under urethane anesthesia). The C57 strain showed higher activity and reactivity expressed by the higher percentage of precise orienting responses after von Frey hair (0.5 g and 5 g) stimulation of various body areas. On the other hand C57 mice were less excitable, as demonstrated by their lower arousability slope index. This dissociation is discussed in terms of neurophysiological and neurochemical mechanisms and of their implications in relation to learning processes.     

Effect of reproductive state on circadian periodicity in the rat

The circadian activity rhythms of adult female rats maintained under a light-dark cycle of 14 hr light, 10 hr dark (LD 14:10) or constant dim illumination (dim LL) were recorded during their 4 or 5 day estrous activity cycles and when they were pseudopregnant. In LD 14:10 both the phase angle difference (ψ), which defines the temporal relationship between the onsets of activity and darkness, and the period (τ) of locomotor activity differed significantly among the days of the 4 and 5 day estrous cycle. Activity-time (α) varied reliably only over the days of the 5 day estrous cycle. The period of the free-running activity rhythm in dim LL also differed significantly among the days of the estrous cycle. In both LD and dim LL the most positive ψ, shortest τ and longest α were observed on the day of estrus. Pseudopregnancy diminished the amplitude and altered the daily pattern of the estrous activity rhythm. We conclude that the periodicity of circadian activity systematically varies as a function of the stage of the estrous cycle and in a manner that cannot be solely explained by corresponding alterations in endogenous estrogen.     

A pilot study of motivational interviewing training in a virtual world

Background

Motivational interviewing (MI) is an evidence-based, patient-centered counseling strategy proven to support patients seeking health behavior change. Yet the time and travel commitment for MI training is often a barrier to the adoption of MI by health care professionals. Virtual worlds such as Second Life (SL) are rapidly becoming part of the educational technology landscape and offer not only the potential to improve access to MI training but also to deepen the MI training experience through the use of immersive online environments. Despite SL’s potential for medical education applications, little work is published studying its use for this purpose and still less is known of educational outcomes for physician training in MI using a virtual-world platform.

Objective

Our aims were to (1) explore the feasibility, acceptability, and effectiveness of a virtual-world platform for delivering MI training designed for physicians and (2) pilot test instructional designs using SL for MI training.

Methods

We designed and pilot tested an MI training program in the SL virtual world. We trained and enrolled 13 primary care physicians in a two-session, interactive program in SL on the use of MI for counseling patients about colorectal cancer screening. We measured self-reported changes in confidence and clinical practice patterns for counseling on colorectal cancer screening, and acceptability of the virtual-world learning environment and the MI instructional design. Effectiveness of the MI training was assessed by coding and scoring tape-recorded interviews with a blinded mock patient conducted pre- and post-training.

Results

A total of 13 physicians completed the training. Acceptability ratings for the MI training ranged from 4.1 to 4.7 on a 5-point scale. The SL learning environment was also highly rated, with 77% (n = 10) of the doctors reporting SL to be an effective educational medium. Learners’ confidence and clinical practice patterns for colorectal cancer screening improved after training. Pre- to post-training mean confidence scores for the ability to elicit and address barriers to colorectal cancer screening (4.5 to 6.2, P = .004) and knowledge of decision-making psychology (4.5 to 5.7, P = .02) and behavior change psychology (4.9 to 6.2, P = .02) increased significantly. Global MI skills scores increased significantly and component scores for the MI skills also increased, with statistically significant improvements in 4 of the 5 component skills: empathy (3.12 to 3.85, P = .001), autonomy (3.07 to 3.85, P < .001), collaboration (2.88 to 3.46, P = .02), and evocative response (2.80 to 3.61, P = .008).

Conclusions

The results of this pilot study suggest that virtual worlds offer the potential for a new medical education pedagogy that will enhance learning outcomes for patient-centered communication skills training.     

Daily rhythm of locomotor activity is abolished during rapid eye movement sleep deprivation in the rat

Applying a modified flowerpot technique, which made it possible to use a test animal as its own control, twenty-four hour cycles of locomotor activity were recorded in eight juvenile male rats on 12/12 hr light/dark (LD) schedule during six days of rapid eye movement (REM) sleep deprivation. It was found that the LD difference in locomotor activity unrelated to feeding was instantaneously abolished during REM sleep deprivation. The daily rhythm of food-directed activity, however, was only gradually attenuated. Due to this equalisation in the light and dark activity the rats gave an impression of hyperactivity during the light hours although the total daily motor output after an initial increase returned close to the baseline value.     

Regulation of scent marking in the female Mongolian gerbil Meriones unguiculatus

The role of estrogens and progesterones in the control of scent marking in the female Mongolian gerbil (Meriones unguiculatus) has remained unclear. Two experiments were conducted which attempted to assess the ovarian contribution to the regulation of this behavioral pattern. In Experiment 1, ten groups of ovariectomized females were treated with one or a combination of steroid hormones which had been selected on the basis of being known secretory products of the ovaries of other rodent species. Only testosterone propionate or a combination of testosterone propionate and estrogen were effective in stimulating marking. Both androgens and estrogens supported gland growth whereas only estrogens supported uterus growth. In a second experiment, androstenedione, a primary precursor to testosterone and estrogen, was administered to intact and ovariectomized females for a period of four weeks. Each female received a weekly marking test following treatment. Intact females responded with a rapid and significant increase in marking frequency whereas ovariectomized and intact control females continued to mark at control levels. It was concluded that the conversion of androstenedione or related hormones into behaviorally active compounds during period of high marking (e.g., as during late gestation and lactation and lactation) is at least one means by which marking is regulated in the female gerbil.     

Effects of sustained-release testosterone on marking behavior in the Mongolian gerbil

Utilizing subcutaneous silastic implants containing testosterone the effect of sustained low-level release of testosterone on marking behavior in castrated Mongolian gerbils was determined. Castration resulted in a decrease in marking frequency from 38 +/- 4 to 4 +/- 1. Sustained release of 6 micrograms testosterone per day from implants did not stimulate marking behavior. Daily release of 11 micrograms increased marking 550% after one week. Release of 17 micrograms per day was required to restore marking to intact levels. Similar release rates of cholesterol did not increase marking. Release rates which increased marking in males did not increase marking in females. The minimum effective sustained-release dose of testosterone necessary to stimulate marking in females was five times greater than that in males. This difference is not due to a sex difference in plasma testosterone removal rates, since the circulating half-life of 3H-testosterone measured by testosterone-specific radioassay was not different in castrated males (72 +/- 5 min) and females (66 +/- 4 min). The present data are consistent with the hypothesis that there is a sexual dimorphism in the testosterone responsiveness of the neural substrate regulating territorial marking behavior.     

Estrogen and progesterone interaction in the regulation of scent marking in the female Mongolian gerbil (Meriones unguiculatus)

Ovariectomized female gerbils were treated with either 0, 20, 40, 80 or 160 μg estradiol benzoate (EB) followed in 36 hr by either 0, 250, 500 or 1000 μg progesterone. The animals were tested for ventral scent marking nine hr after progesterone treatment. Treatment with 20, 40 or 80 μg EB resulted in a significant increase in marking in the ovariectomized female for each dose of progesterone used. One hundred and sixty μg EB was not effective while 80 μg was the most effective dose at each dose of progesterone. There were no differences among the 80 μg EB groups in mean marking frequency as long as progesterone was present. Neither estrogen alone nor progesterone alone was effective in stimulating a significant level of marking. An additional sample of ovariectomized females were maintained for four weeks on either 2.5, 5, 10, 20 or 40 μg EB and tested for marking each week 45 hr after EB administration. On the fifth week 250 μg progesterone was given each week 36 hr following EB with behavioral testing nine hr later. Such a regime was followed for four weeks. Marking remained at zero levels on weeks one through four. EB + progesterone on weeks five through eight, however, resulted in a significant increase in marking in animals receiving 10 μg EB (mean = 9.0 ± 3.5), 20 μg EB (mean = 6.6 ± 2.5) and 40 μg EB (mean = 9.2 ± 4.2). It was concluded that both estrogen and progesterone were essential for the support of marking in this sample of low-marking females and that since there were no reliable differences between groups receiving different doses of progesterone, estrogen was the primary stimulus controlling marking behavior, with progesterone perhaps playing a modifying role.     

Olfactory experience and the development of odor preference and vaginal marking in female Syrian hamsters

Rodent reproductive behavior relies heavily on odor processing, and evidence suggests that many odor-guided sexual behaviors are shaped by prior experience. We sought to determine if exposure to male odors during development is required for the adult expression of proceptive sexual behavior toward male odors in female Syrian hamsters. Exposure to male odors was restricted in na?ve subjects by removing all male siblings from the litter at three to five days of age. Control litters were also culled, but included equal numbers of male and female pups. As adults, na?ve females displayed investigatory preferences toward male odors in a Y-maze that were comparable to control females; this preference was observed whether contact with the odor stimuli was prevented of allowed. In contrast, na?ve females vaginal scent-marked equally toward male and female volatile odors, suggesting an inability to target behavior toward sexually relevant odors. However, na?ve females marked preferentially toward male odors when allowed to contact the odor stimuli. These results provide evidence for the experience-dependent development of vaginal marking behavior toward volatile components of sexual odors. Furthermore, they suggest that distinct mechanisms regulate the development of odor preferences and vaginal marking behavior in this species.     

The AS/AGU rat: a spontaneous model of disruption and degeneration in the nigrostriatal dopaminergic system

The AS/AGU rat provides an alternative to experimentally produced laboratory models of basal ganglia disorders. This mutant is characterised by disturbances of movement including clumsy gait, whole body tremor, rigidity and difficulty in initiating movement. From an early age, there is a profound depletion of extracellular dopamine in the dorsal caudate-putamen as measured via in vivo microdialysis; levels are only 10–20% of those found in the parent Albino Swiss (AS) strain. Subsequently a depletion of whole tissue dopamine levels occurs and, later still, loss of dopaminergic cells in the substantia nigra pars compacta. The dysfunction in movement and the nigrostriatal dopaminergic system are clearly linked, since movement can be ameliorated by L -DOPA administration. Furthermore, there are depletions in glucose utilisation in several regions of the basal ganglia circuitry, including the substantia nigra pars compacta, the subthalamic nucleus and the ventrolateral thalamus. The AS/AGU rat represents a unique opportunity to investigate the intrinsic factors controlling the integrity of dopaminergic systems and the recent successful positional cloning of the agu gene will allow the molecular mechanisms underlying this interesting phenotype to be analysed.     

Fibrinolytic system in the process of wound healing in rat

We investigated the involvement of fibrinolytic system in the process of wound healing as well as angiogenesis in rats using a model system, in which polystyrene capsules with 100 perforated pores filled without (empty capsule) or with fibrin gel (fibrin capsule) were subcutaneously implanted into the dorsal of rats. The intracapsular tissue was accompanied by neovascularization and the tissue weight in the fibrin capsule was three times that of the empty capsule on day 5 after implantation. Both plasminogen activation and amidolytic activities of urokinase-type plasminogen activator (u-PA) in the tissue extracts and intracapsular fluid obtained from the fibrin capsule were higher than those in the empty capsule on day 5 after implantation. Both u-PA and its specific receptor (u-PAR) mRNAs were detected in the intracapsular tissues formed in both capsules. On day 5 after implantation, though the levels of u-PA mRNA in the tissue of the empty capsule and those of the fibrin capsule were not significantly different, more u-PAR mRNA was expressed in the tissue of the fibrin capsule than in the empty capsule. Furthermore, when the cultured endothelial cells were incubated with intracapsular fluids, the proliferation of the cells was significantly enhanced. These results indicate that fibrinolytic activities increase in the presence of fibrin gel, possibly by up-regulation of the u-PA/u-PAR system in the early stage of rat wound healing.     

Oral administration of l-serine reduces the locomotor activity of socially isolated rats

l-Serine is considered a functional amino acid in the central nervous system, since intracerebroventricular injection of l-serine induced sedative and hypnotic effects in neonatal chicks exposed to acute stressful conditions. Accordingly, l-serine is a candidate anti-stress factor, but the effect of daily intake of l-serine on behavior of animals exposed to chronic stress has not been investigated. In the present study, we exposed rats to social isolation stress for 4 weeks, and home cage test and open field test were concluded to evaluate the effect of l-serine on behavior. To investigate l-serine supplementation modifies the brain l-serine and its metabolite contents, free amino acid contents were measured by a high performance liquid chromatography. l-Serine in the drinking water increased l-serine levels in some brain areas, but changes in its metabolites were almost negligible. l-Serine decreased locomotor activity in rats exposed to a familiar environment. In addition, l-serine decreased exploratory behavior of isolated rats, even in a novel environment. Our results could suggest that daily intake of l-serine can attenuate symptoms induced by chronic stress.