Dose-response effects of systemic anandamide administration in mice sequentially submitted to the open field and elevated plus-maze tests

The endocannabinoid system is involved in the control of many physiological functions, including the control of emotional states. In rodents, previous exposure to an open field increases the anxiety-like behavior in the elevated plus-maze. Anxiolytic-like effects of pharmacological compounds that increase endocannabinoid levels have been well documented. However, these effects are more evident in animals with high anxiety levels. Several studies have described characteristic inverted U-shaped dose-response effects of drugs that modulate the endocannabinoid levels. However, there are no studies showing the effects of different doses of exogenous anandamide, an endocannabinoid, in animal models of anxiety. Thus, in the present study, we determined the dose-response effects of exogenous anandamide at doses of 0.01, 0.1, and 1.0 mg/kg in C57BL/6 mice (N = 10/group) sequentially submitted to the open field and elevated plus-maze. Anandamide was diluted in 0.9% saline, ethyl alcohol, Emulphor® (18:1:1) and administered ip (0.1 mL/10 g body weight); control animals received the same volume of anandamide vehicle. Anandamide at the dose of 0.1 mg/kg (but not of 0.01 or 1 mg/kg) increased (P < 0.05) the time spent and the distance covered in the central zone of the open field, as well as the exploration of the open arms of the elevated plus-maze. Thus, exogenous anandamide, like pharmacological compounds that increase endocannabinoid levels, promoted a characteristic inverted U-shaped dose-response effect in animal models of anxiety. Furthermore, anandamide (0.1 mg/kg) induced an anxiolytic-like effect in the elevated plus-maze (P < 0.05) after exposing the animals to the open field test.

Hippocampus lipid peroxidation induced by residual oil fly ash intranasal instillation versus habituation to the open field

Epidemiological studies have demonstrated the adverse effects of particulate matter (PM) inhalation on the respiratory and cardiovascular systems. It has been reported that air pollution may affect the central nervous system and decrease cognitive function. In rats, residual oil fly ash (ROFA) instillation causes decreased motor activity and increased lipid peroxidation in the striatum and the cerebellum. Our objective was to determine whether chronic instillation of particles induces changes in learning and memory in rats and whether oxidants in the hippocampus may contribute to these adverse effects. Forty-five-day-old male Wistar rats were exposed to ROFA by intranasal instillation and were treated with N-acetylcysteine (NAC) at 150 mg/kg i.p. for 30 days. Control groups were exposed to ROFA, NAC, or neither. On days 1, 8, and 30 of the protocol, rats were submitted to the open field test to evaluate habituation. After the last open field session, the rats were killed by decapitation. The hippocampus was used to determine lipid peroxidation (LP) by the thiobarbituric acid-reactive substances test. ROFA instillation induced an increase in LP in the hippocampus compared to all treatment groups (p = .012). NAC treatment blocked these changes. All of the treatment groups presented a decrease in the frequency of peripheral walking (p = .001), rearing (p = .001), and exploration (p = .001) over time. Our study demonstrates that exposure to particles for 30 days and/or NAC treatment do not modify habituation to an open field, a simple form of learning and memory in rats, and that oxidative damage induced by ROFA does not modulate these processes.

Spatial relational learning and memory abilities do not differ between men and women in a real-world, open-field environment

This study assesses gender differences in spatial and non-spatial relational learning and memory in adult humans behaving freely in a real-world, open-field environment. In Experiment 1, we tested the use of proximal landmarks as conditional cues allowing subjects to predict the location of rewards hidden in one of two sets of three distinct locations. Subjects were tested in two different conditions: (1) when local visual cues marked the potentially-rewarded locations, and (2) when no local visual cues marked the potentially-rewarded locations. We found that only 17 of 20 adults (8 males, 9 females) used the proximal landmarks to predict the locations of the rewards. Although females exhibited higher exploratory behavior at the beginning of testing, males and females discriminated the potentially-rewarded locations similarly when local visual cues were present. Interestingly, when the spatial and local information conflicted in predicting the reward locations, males considered both spatial and local information, whereas females ignored the spatial information. However, in the absence of local visual cues females discriminated the potentially-rewarded locations as well as males. In Experiment 2, subjects (9 males, 9 females) were tested with three asymmetrically-arranged rewarded locations, which were marked by local cues on alternate trials. Again, females discriminated the rewarded locations as well as males in the presence or absence of local cues. In sum, although particular aspects of task performance might differ between genders, we found no evidence that women have poorer allocentric spatial relational learning and memory abilities than men in a real-world, open-field environment.

Behavioral Responses in Mice Selectively Bred for High and Low Levels of Open-Field Thigmotaxis

In animal psychology, the open-field (OF) test is a traditional method for studying different aspects of rodent behavior, with thigmotaxis (i.e., wallseeking behavior) being one of the best validated OF parameters employed to measure emotionality. The main purpose of the present study was to investigate the selection response in mice selectively bred for high and low levels of OF thigmotaxis (the HOFT and LOFT lines, respectively). The mice (N = 2048) were selected for 23 generations, resulting in bidirectional phenotypic divergence between the two lines; that is, the HOFT mice were more thigmotactic (i.e., more emotional) than the LOFT mice across the different generations. The origin of the line difference in thigmotaxis was further investigated by using the crossfostering paradigm, with the results suggesting that the divergence between the two lines was primarily innate in origin and not influenced by differing maternal behavior. The stability of the selection trait was examined by testing the animals at different ages as well as in varying conditions. The results indicated that the line difference in thigmotaxis was not affected by age at the time of testing, and it also persisted in the different OF testing situations as well as during pregnancy and lactation. The examination of a possible coselection of other characteristics revealed that the more thigmotactic HOFT mice lived longer than the less thigmotactic LOFT mice. In addition, the HOFT mice tended to rear and explore less than the LOFT mice, supporting the general assumption that emotionality and exploration are inversely related. The two lines did not generally differ in ambulation and defecation, that is, in the traditional OF indexes of emotionality, conforming to the suggestion that emotionality is a multidimensional construct. The effects of sex on different OF parameters were also assessed, with the results suggesting that among the HOFT and LOFT lines, the female mice were more emotional than the male mice. The examination of the temporal changes in the HOFT and LOFT lines’ OF behavior revealed some contradictory findings that also partially conflicted with general assumptions. Although this study did not show prominent differences in maternal responsiveness between the HOFT and LOFT mothers, the results suggested that the line divergence in emotionality was more pronounced in the presence of a pup after parturition than during pregnancy. The present study clearly demonstrates that OF thigmotaxis is a strong characteristic for producing two diverging lines of mice. The difference in thigmotaxis between the selectively bred HOFT and LOFT mice seemed to be a stable and robust feature of these animals, and it appeared to stem from a genetic background.

Pharmacological differences between memory consolidation of habituation to an open field and inhibitory avoidance learning

Rats implanted bilaterally with cannulae in the CA1 region of the dorsal hippocampus or the entorhinal cortex were submitted to either a one-trial inhibitory avoidance task, or to 5 min of habituation to an open field. Immediately after training, they received intrahippocampal or intraentorhinal 0.5-µl infusions of saline, of a vehicle (2% dimethylsulfoxide in saline), of the glutamatergic N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphono pentanoic acid (AP5), of the protein kinase A inhibitor Rp-cAMPs (0.5 µg/side), of the calcium-calmodulin protein kinase II inhibitor KN-62, of the dopaminergic D1 antagonist SCH23390, or of the mitogen-activated protein kinase kinase inhibitor PD098059. Animals were tested in each task 24 h after training. Intrahippocampal KN-62 was amnestic for habituation; none of the other treatments had any effect on the retention of this task. In contrast, all of them strongly affected memory of the avoidance task. Intrahippocampal Rp-cAMPs, KN-62 and AP5, and intraentorhinal Rp-cAMPs, KN-62, PD098059 and SCH23390 caused retrograde amnesia. In view of the known actions of the treatments used, the present findings point to important biochemical differences in memory consolidation processes of the two tasks.

Effects of septal cholinergic lesion on rat exploratory behavior in an open-field

The medial septum participates in the modulation of exploratory behavior triggered by novelty. Also, selective lesions of the cholinergic component of the septohippocampal system alter the habituation of rats to an elevated plus-maze without modifying anxiety indices. We investigated the effects of the intraseptal injection of the cholinergic immunotoxin 192 IgG-saporin (SAP) on the behavior of rats in an open-field. Thirty-nine male Wistar rats (weight: 194-230 g) were divided into three groups, non-injected controls and rats injected with either saline (0.5 µl) or SAP (237.5 ng/0.5 µl). Twelve days after surgery, the animals were placed in a square open-field (120 cm) and allowed to freely explore for 5 min. After the test, the rats were killed by decapitation and the septum, hippocampus and frontal cortex were removed and assayed for acetylcholinesterase activity. SAP increased acetylcholinesterase activity in the septum, hippocampus and frontal cortex and decreased the total distance run (9.15 ± 1.51 m) in comparison to controls (13.49 ± 0.91 m). The time spent in the center and at the periphery was not altered by SAP but the distance run was reduced during the first and second minutes (2.43 ± 0.36 and 1.75 ± 0.34 m) compared to controls (4.18 ± 0.26 and 3.14 ± 0.25 m). SAP-treated rats showed decreased but persistent exploration throughout the session. These results suggest that septohippocampal cholinergic mechanisms contribute to at least two critical processes, one related to the motivation to explore new environments and the other to the acquisition and storage of spatial information (i.e., spatial memory).

Thigmotactic responses in an open-field

The goal of the present study was to investigate the role of thigmotaxis (the tendency to remain close to vertical surfaces) in rat exploratory behavior in an open-field. Thigmotaxis was investigated in a parametric way, using 24 experimentally adult naive male Wistar rats (210-230 g). Exploratory behavior was studied in an open-field (N = 12) in 5-min sessions and behavior was analyzed in terms of where it occurred: in areas surrounded by two, one, or no walls. Another group of rats (N = 12) was studied in an open-field with blocks placed near two of the corners so as to make these corner areas surrounded by three walls. The floor of the open-fields was divided into 20-cm squares in order to locate the exact place of occurrence of each behavior. The following behaviors were recorded: entries into the squares, rearings, and groomings. In both types of open-field the rats chose to remain longer in the squares surrounded by the largest possible number of walls. In one of the open-fields, the mean time (seconds) spent in squares surrounded by two walls was longer than the time spent in squares surrounded by one or no walls (37.2, 7.7, and 1.8 s, respectively). In the other open-field, the mean time spent in squares surrounded by three walls was longer than the time spent in squares surrounded by two, one or no walls (41.7, 20.4, 7.0, and 2.6 s, respectively). Other measures presented a similar profile. These results indicate that rats are sensitive to the number of walls in an environment and prefer to remain close to them.

Dose-response effects of systemic anandamide administration in mice sequentially submitted to the open field and elevated plus-maze tests

The endocannabinoid system is involved in the control of many physiological functions, including the control of emotional states. In rodents, previous exposure to an open field increases the anxiety-like behavior in the elevated plus-maze. Anxiolytic-like effects of pharmacological compounds that increase endocannabinoid levels have been well documented. However, these effects are more evident in animals with high anxiety levels. Several studies have described characteristic inverted U-shaped dose-response effects of drugs that modulate the endocannabinoid levels. However, there are no studies showing the effects of different doses of exogenous anandamide, an endocannabinoid, in animal models of anxiety. Thus, in the present study, we determined the dose-response effects of exogenous anandamide at doses of 0.01, 0.1, and 1.0 mg/kg in C57BL/6 mice (N = 10/group) sequentially submitted to the open field and elevated plus-maze. Anandamide was diluted in 0.9% saline, ethyl alcohol, Emulphor® (18:1:1) and administered ip (0.1 mL/10 g body weight); control animals received the same volume of anandamide vehicle. Anandamide at the dose of 0.1 mg/kg (but not of 0.01 or 1 mg/kg) increased (P < 0.05) the time spent and the distance covered in the central zone of the open field, as well as the exploration of the open arms of the elevated plus-maze. Thus, exogenous anandamide, like pharmacological compounds that increase endocannabinoid levels, promoted a characteristic inverted U-shaped dose-response effect in animal models of anxiety. Furthermore, anandamide (0.1 mg/kg) induced an anxiolytic-like effect in the elevated plus-maze (P < 0.05) after exposing the animals to the open field test.

Ion populations on open field lines within the dayside low-latitude boundary layer: theory and observations during a transient event

We analyze of ion populations observed by the NOAA-12 satellite within dayside auroral transients. The data are matched with an open magnetopause model which allows for the transmission of magnetosheath ions across one or both of the two Alfvén waves which emanate from the magnetopause reconnection site. It also allows for reflection and acceleration of ions of magnetospheric origin by these waves. From the good agreement found between the model and the observations, we propose that the events and the low-latitude boundary precipitation are both on open field lines.

GPR30 activation decreases anxiety in the open field test but not in the elevated plus maze test in female mice

The GPR30 is a novel estrogen receptor (ER) that is a candidate membrane ER based on its binding to 17beta estradiol and its rapid signaling properties such as activation of the extracellular-regulated kinase (ERK) pathway. Its distribution in the mouse limbic system predicts a role for this receptor in the estrogenic modulation of anxiety behaviors in the mouse. A previous study showed that chronic administration of a selective agonist to the GPR30 receptor, G-1, in the female rat can improve spatial memory, suggesting that GPR30 plays a role in hippocampal-dependent cognition. In this study, we investigated the effect of a similar chronic administration of G-1 on behaviors that denote anxiety in adult ovariectomized female mice, using the elevated plus maze (EPM) and the open field test as well as the activation of the ERK pathway in the hippocampus. Although estradiol benzoate had no effect on behaviors in the EPM or the open field, G-1 had an anxiolytic effect solely in the open field that was independent of ERK signaling in either the ventral or dorsal hippocampus. Such an anxiolytic effect may underlie the ability of G-1 to increase spatial memory, by acting on the hippocampus.

EFFECTS OF 2,4-DICHLOROPHENOXYACETIC ACID (2,4-D) ON OPEN-FIELD BEHAVIOR AND NEUROCHEMICAL PARAMETERS OF RATS

The effects of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) on the central nervous system (CNS) were studied in rats. Behavioural and neurochemical studies were performed. Results show that acute and oral administration of dimethylamine 2,4-D was able to decrease locomotion and rearing frequencies and to increase immobility duration of rats observed in an open-field test. Treatment of rats with p-chlorophenylalanine (PCPA) was unable to change rat's open-field behaviour; 5-hydroxytryptophan (5-HTP) administration not only increased locomotion and rearing frequences but also decreased immobility duration. Pretreatment of the rats with PCPA and 5-HTP decreased and increased dimethylamine 2,4-D effects, respectively. The herbicide was not able to change the striatal levels of dopamine and homovanilic acid but decreased the striatal levels of serotonin (5-HT), as observed for the doses of 100 and 200 mg/kg and increased those of 5-hydroxyindoleacetic acid (5-HIAA) as measured after the 200 mg/kg dose treatment. When the levels of serotonin and 5-HIAA were measured at the brain stem level, only those of 5-HIAA were modified, being increased by diethylamine 2,4-D (60; 100 and 200 mg/kg); this increment on 5-HIAA levels was observed even 1 hr after pesticide administration. Further analysis showed that 2,4-D concentrations chromatographycally detected both in serum and brain of the intoxicated animals were dose-dependent, being found as early as 1 hr after the smaller dose of the herbicide used (10 mg/kg). The results suggest that diethylamine 2,4-D modify 5-HT functional activity within the CNS. Thus, the effects of the herbicide on open-field behaviour of rats could be attributed to a direct or indirect pesticide action on serotoninergic systems.

Evaluation of an open-field autorefractor's ability to measure refraction and hence potential to assess objective accommodation in pseudophakes

Background: To evaluate the accuracy of an open-field autorefractor compared with subjective refraction in pseudophakes and hence its ability to assess objective eye focus with intraocular lenses (IOLs). Methods: Objective refraction was measured at 6 m using the Shin-Nippon NVision-K 5001/Grand Seiko WR-5100K open-field autorefractor (five repeats) and by subjective refraction on 141 eyes implanted with a spherical (Softec1 n=53), aspherical (SoftecHD n=37) or accommodating (1CU n=22; Tetraflex n=29) IOL. Autorefraction was repeated 2 months later. Results: The autorefractor prescription was similar (average difference: 0.09±0.53 D; p=0.19) to that found by subjective refraction, with ~71% within ±0.50 D. The horizontal cylindrical components were similar (difference: 0.00±0.39 D; p=0.96), although the oblique (J45) autorefractor cylindrical vector was slightly more negative (by -0.06±0.25 D; p=0.06) than the subjective refraction. The results were similar for each of the IOL designs except for the spherical IOL, where the mean spherical equivalent difference between autorefraction and subjective was more hypermetropic than the Tetraflex accommodating IOL (F=2.77, p=0.04). The intrasession repeatability was

Design and validity of a miniaturized open-field aberrometer

PURPOSE: To validate a new miniaturised, open-field wavefront device which has been developed with the capacity to be attached to an ophthalmic surgical microscope or slit-lamp. SETTING: Solihull Hospital and Aston University, Birmingham, UK DESIGN: Comparative non-interventional study. METHODS: The dynamic range of the Aston Aberrometer was assessed using a calibrated model eye. The validity of the Aston Aberrometer was compared to a conventional desk mounted Shack-Hartmann aberrometer (Topcon KR1W) by measuring the refractive error and higher order aberrations of 75 dilated eyes with both instruments in random order. The Aston Aberrometer measurements were repeated five times to assess intra-session repeatability. Data was converted to vector form for analysis. RESULTS: The Aston Aberrometer had a large dynamic range of at least +21.0 D to -25.0 D. It gave similar measurements to a conventional aberrometer for mean spherical equivalent (mean difference ± 95% confidence interval: 0.02 ± 0.49D; correlation: r=0.995, p<0.001), astigmatic components (J0: 0.02 ± 0.15D; r=0.977, p<0.001; J45: 0.03 ± 0.28; r=0.666, p<0.001) and higher order aberrations RMS (0.02 ± 0.20D; r=0.620, p<0.001). Intraclass correlation coefficient assessments of intra-sessional repeatability for the Aston Aberrometer were excellent (spherical equivalent =1.000, p<0.001; astigmatic components J0 =0.998, p<0.001, J45=0.980, p<0.01; higher order aberrations RMS =0.961, p<0.001). CONCLUSIONS: The Aston Aberrometer gives valid and repeatable measures of refractive error and higher order aberrations over a large range. As it is able to measure continuously, it can provide direct feedback to surgeons during intraocular lens implantations and corneal surgery as to the optical status of the visual system.

Growth and yield of red raspberries cultivated under open field condition vs. high tunnel or rain shelter in the northern canadian climate

La culture sous abris avec des infrastructures de type grands tunnels est une nouvelle technologie permettant d’améliorer la production de framboises rouges sous des climats nordiques. L’objectif principal de ce projet de doctorat était d’étudier les performances de ces technologies (grands tunnels vs. abris parapluie de type Voen, en comparaison à la culture en plein champ) et leur effets sur le microclimat, la photosynthèse, la croissance des plantes et le rendement en fruits pour les deux types de framboisiers non-remontants et remontants (Rubus idaeus, L.). Puisque les pratiques culturales doivent être adaptées aux différents environnements de culture, la taille d’été (pour le cultivar non-remontant), l’optimisation de la densité des tiges (pour le cultivar remontant) et l’utilisation de bâches réfléchissantes (pour les deux types des framboisiers) ont été étudiées sous grands tunnels, abris Voen vs. en plein champ. Les plants cultivés sous grands tunnels produisent en moyenne 1,2 et 1,5 fois le rendement en fruits commercialisables que ceux cultivés sous abri Voen pour le cv. non-remontant ‘Jeanne d’Orléans’ et le cv. remontant ‘Polka’, respectivement. Comparativement aux framboisiers cultivés aux champs, le rendement en fruits des plants sous grands tunnels était plus du double pour le cv. ‘Jeanne d’Orléans’ et près du triple pour le cv. ‘Polka’. L’utilisation de bâches réfléchissantes a entrainé un gain significatif sur le rendement en fruits de 12% pour le cv. ‘Jeanne d’Orléans’ et de 17% pour le cv. ‘Polka’. La taille des premières ou deuxièmes pousses a significativement amélioré le rendement en fruits du cv. ‘Jeanne d’Orléans’ de 26% en moyenne par rapport aux framboisiers non taillés. Des augmentations significatives du rendement en fruits de 43% et 71% du cv. ‘Polka’ ont été mesurées avec l’accroissement de la densité à 4 et 6 tiges par pot respectivement, comparativement à deux tiges par pot. Au cours de la période de fructification du cv. ‘Jeanne d’Orléans’, les bâches réfléchissantes ont augmenté significativement la densité de flux photonique photosynthétique (DFPP) réfléchie à la canopée inférieure de 80% en plein champ et de 60% sous grands tunnels, comparativement à seulement 14% sous abri Voen. Durant la saison de fructification du cv. ‘Polka’, un effet positif de bâches sur la lumière réfléchie (jusqu’à 42%) a été mesuré seulement en plein champ. Dans tous les cas, les bâches réfléchissantes n’ont présenté aucun effet significatif sur la DFPP incidente foliaire totale et la photosynthèse. Pour le cv. ‘Jeanne d’Orléans’, la DFPP incidente sur la feuille a été atténuée d’environ 46% sous le deux types de revêtement par rapport au plein champ. Par conséquent, la photosynthèse a été réduite en moyenne de 43% sous grands tunnels et de 17% sous abris Voen. Des effets similaires ont été mesurés pour la DFPP incidente et la photosynthèse avec le cv. Polka. En dépit du taux de photosynthèse des feuilles individuelles systématiquement inférieur à ceux mesurés pour les plants cultivés aux champs, la photosynthèse de la plante entière sous grands tunnels était de 51% supérieure à celle observée au champ pour le cv. ‘Jeanne d’Orléans’, et 46% plus élevée pour le cv. ‘Polka’. Ces résultats s’expliquent par une plus grande (près du double) surface foliaire pour les plants cultivés sous tunnels, qui a compensé pour le plus faible taux de photosynthèse par unité de surface foliaire. Les températures supra-optimales des feuilles mesurées sous grands tunnels (6.6°C plus élevé en moyenne que dans le champ), ainsi que l’atténuation de la DFPP incidente (env. 43%) par les revêtements de tunnels ont contribué à réduire le taux de photosynthèse par unité de surface foliaire. La photosynthèse de la canopée entière était étroitement corrélée avec le rendement en fruits pour les deux types de framboisiers rouges cultivés sous grands tunnels ou en plein champ.

Identifying the Open-Closed Field Line Boundary

Of all the various definitions of the polar cap boundary that have been used in the past, the most physically meaningful and significant is the boundary between open and closed field lines. Locating this boundary is very important as it defines which regions and phenomena are on open field lines and which are on closed. This usually has fundamental implications for the mechanisms invoked. Unfortunately, the open-closed boundary is usually very difficult to identify, particularly where it maps to an active reconnection site. This paper looks at the topological reconnection classes that can take place, both at the magnetopause and in the cross-tail current sheet and discusses the implications for identifying the open-closed boundary when reconnection is giving velocity filter dispersion of signatures. On the dayside, it is shown that the dayside boundary plasma sheet and low-latitude boundary layer precipitations are well explained as being on open field lines, energetic ions being present because of reflection of central plasma sheet ions off the two Alfvén waves launched by the reconnection site (the outer one of which is the magnetopause). This also explains otherwise anomalous features of the dayside convection pattern in the cusp region. On the nightside, similar considerations place the open-closed boundary somewhat poleward of the velocity-dispersed ion structures which are a signature of the plasma sheet boundary layer ion flows in the tail.