Risk assessment behaviour: evaluation of utility in the study of 5-HT-related drugs in the rat elevated plus-maze test

The present study compared the effects of a wide range of 5-hydroxytryptamine (5-HT)-modulating and potential anxiolytic agents in the rat elevated plus-maze using spatiotemporal (i.e., open arm time and entries) and ethologically derived measures (i.e., risk assessment activities and directed exploration). The drugs used were 5-HT1A receptor partial (buspirone and ipsapirone) and full (8-OH-DPAT and flesinoxan) agonists, mixed 5-HT2A/2C receptor antagonists (ritanserin, ketanserin, mianserin, and pirenperone), selective 5-HT3 receptor antagonists (ICS 205-930, MDL 72222, ondansetron, and (RS)-zacopride), and selective (fluoxetine, fluvoxamine, and zimelidine) and nonselective (imipramine) 5-HT reuptake inhibitors. Only buspirone and mianserin produced effects indicative of an anxiolytic-like action on the spatiotemporal measures. However, all 5-HT1A receptor ligands, as well as mianserin, ketanserin, ondansetron, and zacopride, decreased the number of aborted attempts at entry into open arms (risk assessment). In addition, buspirone, mianserin, and zacopride increased head-dipping (directed exploration). Among the 5-HT reuptake inhibitors, zimelidine reduced head-dipping and total entries. The present findings demonstrate that risk assessment responses are sensitive to the action of 5-HT1A receptor ligands, but their modulation by drugs targetting 5-HT2A, 5-HT2C, and 5-HT3 receptors was not convincingly established.     

Hippocampal histamine receptors and conflictive exploration in the rat: studies using the elevated asymmetric plus-maze

The possible role of histamine receptors in the hippocampal formation on the exploratory motivation and emotionality of the rat was studied. An elevated asymmetric plus-maze composed of 4 different arms (no walls, single high wall, high and low walls and two high walls) arranged at 90 degrees angles was used. The exploration score, considered to be an index of exploratory motivation, and the permanency score, considered to be an index of emotionality (anxiety), were determined. Histamine was administered locally into the ventral hippocampus at three different doses (9, 45 and 90 nmol). Another group of rats was also microinjected with 45 nmol of pyrilamine (a histamine H1 receptor antagonist) or ranitidine (a histamine H2 receptor antagonist) in addition to 9 nmol of histamine in order to identify the possible type of histamine receptor involved. Histamine administration significantly inhibited the exploration score and increased the permanency score at the doses of 9 and 45 nmol in two of four arms. These effects were completely blocked by the administration of either histamine receptor antagonist. The present results suggest that in the hippocampal formation histamine inhibits exploratory motivation and decreases emotionality by activating both types of histamine receptors. Also, the elevated asymmetric plus-maze appears to be a suitable technique to quantify exploration and possibly "anxiety".     

Rat strain differences in copulatory behavior after para-chlorophenylalanine and hormone treatment.

The potentiation of masculine copulatory behavior in castrated male rats following systemic parachlorophenylalanine (PCPA) treatment was found to be dependent upon the strain of rat and the recency of castration. Wistar (W) and Sprague-Dawley (SD) males displayed a decline in behavioral responsiveness to PCPA treatment following castration, the Ws retaining their behavioral responsiveness longer than SDs. Castrated Ws were also behaviorally more responsive to androgen replacement than were SDs. Ovariectomized W and SD females receiving estrogen replacement displayed a strain difference in hormonal sensitivity. In tests for feminine copulatory behavior, ovariectomized Ws were behaviorally more sensitive to estrogen treatment than SDs. Ovariectomized and estrogen-primed females of both strains displayed potentiated lordotic behavior following chronic PCPA treatment. Concomitant treatment with dexamethasone to reduce adrenal steroid output abolished the potentiation of lordotic behavior found with PCPA treatment. (47 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Flow cytometry as a sensitive tool to assess testicular damage in rat

The aim of this study was to compare results obtained by flow cytometry (FCM) with those obtained from testicular histopathology with regard to testicular damage following acute exposure of adult rats to the known testicular toxicant, methoxyacetic acid (MAA). Special emphasis was given to defining the sensitivity of three-parameter FCM compared with testicular histopathology. Furthermore, the effect on the male reproductive system of a single oral dose of MAA was evaluated with traditional methods, e.g. testicular sperm head counts, and organ weights. Adult, male Han/Wistar rats were randomly assigned to four groups of ten animals to be treated with a single dose of 0, 65, 325 and 650 mg MAA/kg body wt. (p.o., gavage). The animals were killed 2 days after treatment, and testicular and epididymal weights were recorded. One testis and the corresponding epididymis were used for histopathology. The other testis was used partly to determine sonication-resistant, testicular sperm-head counts (SHC), and partly for enzymatic digestion followed by FCM. The results obtained in this study are in agreement with the literature, and show that, in the adult male rat, 2 days after administering a single oral dose of MAA, specific depletion of spermatocytes is evident. Detectable testicular effects were produced by the high (650 mg/kg body wt.) and mid (325 mg/kg body wt.) doses, whilst the low dose (65 mg/kg body wt.) did not produce any noticeable effect. There was a strong correlation between results obtained by FCM and those obtained by testicular histopathology, and no difference in sensitivity between the two methods was observed. In summary, three-parameter FCM represents a sensitive and reliable method for the detection of testicular injury in the rat. It requires only small amounts of tissue, and the sensitivity was shown to be similar to that of histopathology. Moreover, FCM has the advantages of being quick and objective, which permits large numbers of cells to be analysed. The potential use of this method as a fast screening tool for testicular toxicity in routine toxicology studies should be considered.     

Ethological analysis of cholecystokinin (CCKA and CCKB) receptor ligands in the elevated plus-maze test of anxiety in mice

Membranes for determination of maltose, lactose and sucrose with the use of an oxygen electrode are described. They were obtained by immobilization of glucose oxidase with suitable disaccharide hydrolase in gelatin or albumin. For the sucrose determination mutarotase was also used. The membranes contained one, two or three enzymes working in sequence. The enzyme composition of the membranes influenced the linear range slightly and the value of electrode response considerably. The electrode response of the maltose membranes was also affected by the immobilization material. The measurements with the use of enzymatic membranes were very sensitive to temperature and, to some degree, the pH of the sample. Stability of the membranes was differentiated. The albumin membranes for sucrose determination generated almost the same signal after 1 month of frequent use, whereas the gelatin membranes for lactose determination lost about 85% of the initial activity after 1 week of operation. The electrode response of both the gelatin and albumin maltose membranes decreased in the same time by about 50%.     

Preferred position of visual displays relative to the eyes: a field study of visual strain and individual differences

At office workplaces equipped with visual display units (VDU) that were adjustable to various positions relative to the eyes short and long viewing distances from the eyes to the screen were imposed (mean value of about 63 and 92 cm) at two levels of screen height so that the visual target was either at eye level or 18 cm below, on the average. The change from far to near viewing distance produced a larger increase in eyestrain when the VDUs were at eye level. High screens resulted in greater eyestrain than low screens, as shown by correlations over subjects. When operators were free to adjust the most comfortable screen position, the group of 22 participants preferred viewing distances between 60 and 100 cm and vertical inclination of gaze direction between horizontal and -16 degrees downwards. However, within most subjects the range of preferred screen positions was much smaller. Between 3 days during a 1-month period the test-retest correlations of the preferred screen positions were highly significant, both for viewing distance and vertical gaze inclination. When operators were forced to work at a shorter distance than their preferred viewing distance they reported more visual strain. Thus, operators appear to prefer an individual adjustment of the screen relative to the eyes in order to avoid visual strain and discomfort at VDU work.     

Mouse strain differences in apomorphine-induced behavior: An empirical and methodological study.

Evaluated the behavioral response to intraperitoneal apomorphine HCl (0.5–32 mg/kg) in BALB/cJ, CBA/J, and C57BL/6J male mice. Dose–response curves for each component of the drug-induced behavioral repertoire were derived, and effective dose-50 (the dose at which 50% of the Ss met or exceeded a given rating) and slope were calculated for each. This method of analysis allows for a more quantitative estimate of drug sensitivity. Behaviors assessed included grooming, sniffing, climbing, and gnawing. Although some strain differences were observed in the qualitative characteristics of the response, differences in actual drug sensitivity were significant only at the higher ratings. Findings are discussed in relation to methodological and analytical problems in previous strain-comparison experiments. (31 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Repeated trials with the albino rat in the open field as a function of age and deprivation.

Each of 3 experiments demonstrated that female Sprague-Dawley albino juvenile rats (n = 24) become increasingly active during 10 consecutive trials in the open field; adults (n = 24) did not show this day-to-day change. Age-related activity change was unaffected by food deprivation and is interpreted to be a consequence of the greater curiosity and ease in familiarization with a novel environment among juveniles. The greater intensity of ambulation among immature Ss may provide an explanation for age-related differences in appetitive learning. (24 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Improvement by FUB 181, a novel histamine H3-receptor antagonist, of learning and memory in the elevated plus-maze test in mice

PURPOSE: Initial experimental results of contrast-enhanced pulmonary MR angiography using the new superparamagnetic iron oxide blood pool agent FeO-BPA. METHOD: Pulmonary MRA was performed in 7 domestic pigs using a cardiac-triggered coronal T1-weighted FFE-Sequence before and up to 90 minutes after contrast injection obtained on a 1.5 T magnet with a standard gradient equipment. A dose of 4 mg Fe/kg bodyweight was used for MRA. The images were qualitatively assessed and compared with X-ray i.v.-DSA. RESULTS: The injection of FeO-BPA allows the acquisition of unsaturated in-plane images of the pulmonary vascular tree down to the first order subsegmental branches including vessel diameters of approximately 1.5 mm. In the normal non-occluded vasculature, no signal void is seen in the TE range of 2.8-5.5 ms secondary to exceeding susceptibility effects which are caused by the iron oxide accumulation. Even 90 minutes after injection of FeO-BPA, assessment of the pulmonary vasculature is still satisfactory. CONCLUSIONS: In the animal experiment, the use of the blood pool agent FeO-BPA provides detailed pulmonary angiograms even on a magnet with a conventional gradient system. The major advantage is the comfortable diagnostic window of > 1.5 hours which also portends its utility for future MR-guided pulmonary interventions.     

Immune responses in male mice with aggressive and submissive behavior patterns: strain differences

Geminiviruses are being used as convenient autonomously replicating vectors for foreign gene amplification in plants. Using tissue culture techniques, they have been adapted for the analysis of the regulation of gene expression in a wide range of hosts, including both mono- and dicotyledonous species. In monocotyledonous plants that are particularly recalcitrant to transformation, geminivirus symptom-induction has been used as a sensitive marker for DNA uptake.     

Failure to find differences in drinking behavior as a function of familial risk for alcoholism: A replication.

Groups of high-risk (alcoholic fathers), middle-risk (second-degree alcoholic relatives) and low-risk (no first- or second-degree alcoholic relatives) male college students were compared with respect to drinking behavior, sociodemographic variables, personality, cognitive functioning, and mental health and drug use problems in themselves and in family members. The groups differed significantly on only one of a number of sociodemographic variables. No significant group differences were revealed in drinking behavior, or alcohol-related symptoms or consequences. High-risk subjects reported significantly more childhood attentional and social problems than did low-risk subjects. No group differences were found with respect to other childhood problem behaviors, cognitive functioning, subject or family drug use, or mental health problems. The findings are discussed in terms of the questions they raise concerning the results of high-risk studies and the contribution of genetic factors to alcoholism. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stressor predictability influences open field behavior, pain sensitivity and brain MAO inhibitory activity (tribulin) in the rat

PURPOSE: To determine whether histologic findings of cancer or atypical hyperplasia at large-core needle biopsy (LCNB) of nonpalpable breast lesions match histologic findings at excision. MATERIALS AND METHODS: Stereotaxic LCNB was performed with an automated prone unit, biopsy gun, and 14-gauge cutting needles in 450 nonpalpable breast lesions. Lesions classified as carcinoma or atypical ductal hyperplasia (ADH) at histologic examination after LCNB were excised. A pathologist retrospectively compared core and excisional histologic findings. RESULTS: Histologic comparison was performed in 116 of 135 carcinomas after LCNB. Histologic findings were concordant in 99 carcinomas. Partial discordance in 17 carcinomas led to an additional surgical procedure in one case. Histologic comparison was performed in 16 of 19 ADHs diagnosed with LCNB. Histologic findings were concordant in five and discordant in 11 ADHs. CONCLUSION: LCNB findings of carcinoma are accurate and allow definitive therapeutic surgery, including mastectomy. LCNB findings of ADH are inaccurate, and excisional biopsy is necessary.     

Developmental differences in responses to a television character's appearance and behavior.

In a 2?×?2?×?3 design, 52 3–5 yr olds, 58 6–7 yr olds, and 59 9–10 yr olds viewed a videotape in which a female protagonist's appearance (attractive, ugly) was factorially varied with her behavior (kind, cruel). Perceptions of the protagonist and predictions of the story's outcome were assessed. Based on theoretical and empirical evidence of a developmental decrease in perceptual dependence, the influence of the woman's appearance was expected to decrease with age, and the influence of her behavior was expected to increase with age. These expectations were confirmed. A 2nd study was conducted with 40 4–5 yr olds, 41 6–7 yr olds, and 34 9–21 yr olds to rule out the alternative explanation that younger children possess stronger physical appearance stereotypes than do older children. In this study, Ss did not have information about the woman's behavior. It was found that Ss at all 3 age levels demonstrated appearance stereotyping. (36 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Age differences in the nature and origin of individual differences in memory: a behavior genetic analysis

Acrylonitrile (ACN) exposure is associated with tumors in rat brain, Zymbal gland, and mammary gland. Adducts affecting base pairing were formed in isolated DNA exposed in vitro to the ACN metabolite cyanoethylene oxide (CNEO). DNA from liver, which is not a cancer target organ in ACN-exposed rats, contained low levels of 7-(2-oxoethyl)guanine, and adduct believed not to interfere with base pairing. No adducts have been detected in brain DNA from ACN-exposed rats, suggesting that brain tumors may have arisen by mechanisms other than ACN-DNA reactivity. Genotoxicity assays of ACN have indicated no particular carcinogenic mechanism. Positive reverse mutagenesis in Salmonella typhimurium HisG46 base substitution tester strains by ACN is attributable to CNEO. Other in vitro genotoxicity test assays of ACN have yielded mixed results, without consistent effect of metabolic activation. Some positive genotoxicity data for ACN appear to result from artifacts or from non-DNA-reactive mechanisms. In vivo micronucleus, chromosome aberration, and autoradiographic unscheduled DNA synthesis assays were negative for ACN. The comparative genotoxicity of vinyl chloride and ACN indicates that despite other similarities, they cause rodent tumors by different mechanisms. Also, they absence of ACN-DNA adduct formation in the rat brain suggests the operation of epigenetic mechanisms.     

The role of individual differences in field dependence as a factor in learning and memory.

A review of the literature relating individual differences in field dependence to learning and memory suggests the following conclusions: (a) Field-dependent Ss are dominated by the salient cues in concept attainment problems, whereas field-independent Ss sample more fully from the available cue set. (b) Field-dependent Ss tend to use "spectator" approaches to learning. Whereas field-independent Ss more often use "participant" approaches. (c) Field independence is related to frequency of dream recall. (d) Field dependence is related to the magnitude of stress effects on learning and memory. (e) Field independence is related to performance effectiveness under conditons of intrinsic motivation. (f) Field dependence is related to the effectiveness of negative reinforcement. (g) Incidental learning of social information is greater among field-dependent than among field-independent Ss. (5 p ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A new tool to assess treatment fidelity and evaluation of treatment fidelity across 10 years of health behavior research.

A. Bellg, B. Borrelli, et al. (2004) previously developed a framework that consisted of strategies to enhance treatment fidelity of health behavior interventions. The present study used this framework to (a) develop a measure of treatment fidelity and (b) use the measure to evaluate treatment fidelity in articles published in 5 journals over 10 years. Three hundred forty-two articles met inclusion criteria; 22% reported strategies to maintain provider skills, 27% reported checking adherence to protocol, 35% reported using a treatment manual, 54% reported using none of these strategies, and 12% reported using all 3 strategies. The mean proportion adherence to treatment fidelity strategies was .55; 15.5% of articles achieved greater than or equal to .80. This tool may be useful for researchers, grant reviewers, and editors planning and evaluating trials. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Food wrenching and dodging: A neuroethological test of cortical and dopaminergic contributions to sensorimotor behavior in the rat.

Sensorimotor behavior in unilateral decorticate and unilateral dopamine-depleted rats was studied in a naturally occurring social interaction in which rats compete for food with relatively stereotyped species-typical responses. In the interaction a "robber" attempts to wrest food from a feeding "victim," which in turn protects the food by making rapid contralateral dodges. Hemidecortication abolished dodging to food wrenching attempts made by a rat approaching contralaterally to the lesion, so that the food was stolen, but recovery occurred between 15 and 60 days after surgery. Use of the side contralateral to the lesion to wrest food was moderately impaired, and recovery of food wresting was more rapid than recovery of dodging. Unilateral dopamine depletion produced dodging impairments to food-wresting attempts that were made both ipsilateral and contralateral to the side of the lesion, and the deficits endured over 60 test days. The food was frequently lost to food-wrenching attempts made contralateral to the lesion, whereas the direction of dodges to approaches ipsilateral to the lesion was reversed. Food wresting was also bilaterally impaired. (PsycINFO Database Record (c) 2010 APA, all rights reserved)