Open-field Behavior In Rats Research Articles

Ethovision™ analysis of open field behaviour in rats following bilateral vestibular loss.

Bilateral vestibular loss (BVL) causes a unique behavioural syndrome in rodents, with symptoms such as locomotor hyperactivity and changes in exploratory behaviour. Many of these symptoms appear to be indirect consequences of the loss of vestibular reflex function and are difficult to explain. Although such symptoms have been reported before, there have been few systematic studies of the effects of BVL using automated digital tracking systems in which many behavioural symptoms can be measured simultaneously with high precision. In this study, data were obtained from rats with BVL induced by intratympanic sodium arsanilate injections (n = 7) or sham injections (n = 8) and their behaviour in the open field was measured at 3 days and 23 days post-injection using Ethovision™ tracking software. BVL rats demonstrated reduced thigmotaxis, with more time spent in the central zones. Twenty-three days post-injection, BVL animals showed increased locomotor activity in the open field. The increase in activity was also reflected in the number of transitions between each zone of the field. In addition to increased activity, BVL animals showed increased whole body rotations following lesions. Using linear discriminant analysis (LDA) and random forest classification (RFC), we were able to show that the indirect behavioural effects of BVL, excluding direct measurement of vestibular reflex function, could correctly predict whether animals had received a BVL with a high degree of accuracy at both day 3 and day 23 post-BVL (83% and 100% for LDA, and 100% and 100% for RFC, respectively). RFC has been similarly successful in classifying other hyperactivity syndromes such as attention deficit hyperactivity disorder. These results suggest that BVL results in a unique behavioural signature that can identify vestibular loss in rats even without direct vestibular reflex measurements.

Propentofylline treatment on open field behavior in rats with focal ethidium bromide-induced demyelination in the ventral surface of the brainstem

Propentofylline (PPF) is a xanthine derivative with pharmacological effects that are distinct from those of classic methylxanthines. It depresses the activation of microglial cells and astrocytes, which is associated with neuronal damage during neural inflammation and hypoxia. Our previous studies showed that PPF improved remyelination following gliotoxic lesions that were induced by ethidium bromide (EB). In the present study, the long-term effects of PPF on open field behavior in rats with EB-induced focal demyelination were examined. The effects of PPF were first evaluated in naive rats that were not subjected to EB lesions. Behavior in the beam walking test was also evaluated during chronic PPF treatment because impairments in motor coordination can interfere with behavior in the open field. The results showed that PPF treatment in unlesioned rats decreased general activity and caused motor impairment in the beam walking test. Gliotoxic EB injections increased general activity in rats that were treated with PPF compared with rats that received saline solution. Motor incoordination was also attenuated in PPF-treated rats. These results indicate that PPF reversed the effects of EB lesions on behavior in the open field and beam walking test.

Low-dose oral caffeine induces a specific form of behavioral sensitization in rats

AbstractThe present study assessed the effects of a low dose of orally administered caffeine on sensitization of open-field behavior in rats. Rats had free access to untreated water every day or water containing 0.2mg/ml of caffeine every other day of the 14-day experiment. On alternate days discrete movements (horizontal and vertical) and ambulatory distance were measured in open-field activity monitors. Although caffeine intake significantly decreased across test sessions in caffeine-treated rats, the number of discrete horizontal movements significantly increased. These findings suggest that low doses of orally administered caffeine induce a specific form of behavioral sensitization in rats.

Poster 97 Repeated Blast Exposure Alters Open Field Behavior in Rats

Poster 97 Repeated Blast Exposure Alters Open Field Behavior in Rats

Dietary lutein improves episodic memory in young rats

Human milk is considered the ideal source of nutrition for optimal infant development. Lutein is a carotenoid nutrient found in human milk and has recently been added to infant formula. Lutein is a component of human retina, and has also been co‐localized to human brain regions. We have previously reported that lutein significantly increases the length of neurites on rat primary hippocampal neurons. The purpose of this work was to determine if this morphological effect of lutein is associated with an enhancement of cognitive function. Here, we report the impact of early postnatal dietary lutein on rat open‐field behavior and novel object recognition. Weanling Long‐Evans rats were fed AIN‐93G based diets formulated to contain 0 mg/kg lutein, 2.5 mg/kg lutein, or 250 mg/kg lutein for 36 days. Diet treatments were blinded to the investigators and behaviors were quantified by automated video tracking software (Noldus). No significant differences were observed between treatment groups on any open‐field behavioral outcomes, suggesting no motor or anxiety related effects due to diet. Importantly, 48 hours after acquisition of two identical objects, rats fed 250 mg/kg lutein spent significantly more time investigating the novel object (p=0.01) while rats fed 0 or 2.5 mg/kg diet did not show novel object recognition (p=0.97 and p=0.84 respectively). These data suggest that dietary lutein improves episodic memory in rats.

The effect of the NMDA receptor antagonist dizocilpine on behavioral manifestations of serotonin and adrenergic antidepressants in rats

Glutamatergic neurotransmission has been implicated in affective disorders, possibly through the modulation of monoaminergic mechanisms. The aim of this study was to investigate the effect of coadministration of the noncompetitive NMDA antagonist dizocilpine (MK-801) with different, primarily noradrenergic and serotonergic antidepressants on forced swimming test (FST) and open-field behavior in rats. Acute administration of dizocilpine at doses of 0.02- 0.1 mg/kg did not show any effect in the open-field test or FST. Acute administration of citalopram (5 mg/kg), fluoxetine (20 mg/kg), desipramine (20 mg/kg) and maprotiline (20 mg/kg) did not influence FST, although coadministration of dizocilpine with serotonergic but not noradrenergic antidepressants caused a significant reduction of immobility. In the open-field test, fluoxetine had no effect on horizontal activity but significantly reduced the number of rearings. The coadministration of dizocilpine with fluoxetine elicited significant horizontal locomotor activation and attenuated the effect of fluoxetine on vertical activity. The combined administration of other antidepressants with dizocilpine tended to increase horizontal activity similar to that recorded with fluoxetine plus dizocilpine, but these effects were not statistically significant. Thus, the present results indicated that the coadministration of serotonergic antidepressants with NMDA receptor antagonists may induce faster and more pronounced antidepressant activity when compared to treatment with antidepressants alone. In contrast, the NMDA antagonists did not potentiate the antidepressant-like effects of noradrenergic antidepressants.

Altered open field behavior in rats induced by acute administration of 3-nitropropionic acid: Possible glutamatergic and dopaminergic involvement

3-nitropropionic acid (3-NP), a substance used for modelling Huntington's disease, was given to male Wistar rats in a single 20 mg/kg b.w. dose, and the resulting behavioral alterations in spontaneous locomotor activity were measured after 30 minutes. To detect the involvement of neurotransmitter systems in this immediate effect, the NMDA antagonist MK-801 (0.8 mg/kg); as well as an agonist, quinpirole (QP, 5 mg/kg) and an antagonist, sulpiride (SP, 80 mg/kg) of the dopamine D2 receptors, were given before 3-NP to separate groups of rats. Controls were given saline. All substances were injected ip. 3-NP decreased the rats' locomotor, especially vertical, activity, whereas local activity was increased. Based on the further changes of 3-NP effects in the combination groups it could be concluded that dopaminergic rather than glutamatergic mechanisms were possibly involved in the acute behavioral effect of 3-NP.

Urocortin 1 administered into the hypothalamic supraoptic nucleus affects open-field behaviour in rats

The presence of both Urocortin 1 (Ucn1) and corticotropin-releasing factor 2 receptors (CRF(2)R) in the hypothalamic supraoptic nucleus (SON) suggests that endogenous Ucn1 released within this brain area acts as a local signal that might be involved in the regulation of not only endocrine but also behavioural stress responses. To test this hypothesis, we monitored the effects induced by the administration of a range of doses of synthetic Ucn1 (0.001-1.0 microg) bilaterally into the SON of rats in the open field test (OFT). Ucn1 administration produced an inverted U-shaped dose-response curve on OFT behaviour, in particular the dose of 0.01 microg of Ucn1 significantly increased the number of rearing and grooming episodes without affecting locomotion. In addition, this dosage augmented also the latency to visit the centre of the open field. Pre-treatment with the CRF(2)R antagonist, astressin-2B (0.1 microg) normalized Ucn1 treatment-induced effects. These results suggest that Ucn1 released within the SON area interacts with CRF(2)R to control the state of arousal.

Time-dependent effects of striatal interleukin-2 on open field behaviour in rats

There is evidence that immune messengers like cytokines can modulate emotional and motivated behaviours and are involved in psychiatric conditions like anxiety, and depression. Previously, we showed that cytokine gene expression (interleukin (IL)-2 mRNA) in specific brain tissues (striatum, prefrontal cortex) correlated with anxiety-like behaviour (open arm time) in an elevated plus-maze in rats. In a subsequent experiment, a single striatal IL-2 injection showed behavioural trends with the lower dose (1 ng) acting in a behavioural suppressive way, whereas the highest dosage (25 ng) led to activation and anxiolytic-like behaviour. Here, to support and extend our previous findings, we tested Wistar outbred rats after a single unilateral (balanced brain sites) IL-2 injection into the ventral/dorsal striatum followed by an open field test acutely and 24 h later. Analyses for horizontal locomotion showed no differences between groups. However, rats with IL-2-treatment (0.1 ng) showed a dose-dependent avoidance effect (i.e. reduced centre time) compared to the 1 ng group and vehicle controls 24 h later. In addition, suppression of free rearing activity was shown for both IL-2 doses (0.1; 1 ng) compared to saline in the acute test, and partly 24 h later. Thus, in experiment 2, we tested for proactive drug mechanisms to test for delayed effects of IL-2 as observed in experiment 1. In a new sample, rats were returned to their home cages after a striatal IL-2 injection (0.1; 0.01; 0 ng), and tested 24 h and 48 h after the injection in an open field. Neither for the first (24 h) nor for the second exposure (48 h later) did the analyses show any significant behavioural effects. We therefore suggest that emotional-related behaviour can be modulated by striatal IL-2 for at least 24 h. However, such IL-2 effects can only be observed if a mild stressful environmental challenge (i.e., forced open field exposure) is followed immediately after injection. In conclusion, proactive drug effects may be excluded for striatal IL-2 effects on open field behaviour.

A double exposure to social defeat induces sub-chronic effects on sleep and open field behaviour in rats

Social defeat, resulting from the fight for a territory is based on the resident–intruder paradigm. A male rat intruder is placed in the territory of an older, bigger and more aggressive male resident and is defeated. In the present study, a double exposure to social defeat increased sleep fragmentation due to an increased amount of waking and slow-wave-sleep-1 (SWS-1) episodes. Also, social defeats increased the amount of slow-wave-sleep-2 (SWS-2). In repeated exposures to an open field, socially defeated rats showed low central activity and persistent defecation indicating high emotionality. The strongest effects of social defeat on sleep and open field behaviour were seen sub-chronically after stress. Social defeat did not induce changes in rapid eye movement (REM) sleep (e.g. total amount, latency), sleep latency, sexual activity, body weight or adrenal weight. A negative correlation between habituation in open field central activity and total sleep fragmentation indicates a commonality of effects of social defeat on both behaviour and sleep.

Open field behavior and habituation in rats irradiated on the head with gamma-rays

The goal of this work was to establish the effects of irradiation of the head with gamma-rays on selected forms of innate behavior, as well as on the habituation process to new environment in the open field test in rats. During a 5-day control period behavioral parameters reflecting motoric and explorative activities, as well as anxiety (6 parameters in total) were followed daily in 20 male Sprague-Dawley rats in an open field. Fourteen animals were repeatedly tested after irradiation of the head with a single dose of 10 Gy of gamma-rays. The results showed statistically significant depression of motoric and explorative activities during the first 3 days after irradiation in comparison with the control period. After irradiation the level of anxiety was elevated. Habituation to a new environment was observed in non-irradiated, but not in irradiated animals. These results suggest that the applied dose of ionizing radiation influenced the brain centers involved in control of innate behavioral functions connected with response to a new environment in rats.

Effects of AM1346, a high-affinity CB1 receptor selective anandamide analog, on open-field behavior in rats

AM1346 is a cannabinoid receptor type 1 (CB1R) anandamide analog [alkoxyacid amide of N-eicosa-(5Z, 8Z, 11Z, 14Z)-tetraenylamine] with high affinity and selectivity for the CB1 vs. CB2 receptor [Ki (CB1)=1.5 nmol/l; Ki (CB2)=152 nmol/l]. The present study characterized the effects of AM1346 (5.6-18 mg/kg) and its interaction with the CB1R antagonist/inverse agonist SR141716 (1-5.6 mg/kg) on open-field behaviors of rats. AM1346 reduced ambulation (horizontal activity), rearing (vertical activity) and increased the degree of circling and the latency to leave the central area of the open-field arena. AM1346 also tended to reduce defecation and to increase vocalization in a dose-dependent manner. In pretreatment studies, SR141716 completely blocked the effects of AM1346 on circling and latency and partially antagonized the effects of 18 mg/kg AM1346 on ambulation and rearing. SR141716 also tended to decrease AM1346-induced vocalization in a dose-dependent manner. Earlier studies have shown that SR141716, given alone, can increase grooming behavior and, as well, produces dose-related increases in scratching. In the present studies, these effects were attenuated in a dose-related manner by AM1346. The present profile of behavioral effects for AM1346 is consistent with its designation as a CB1R agonist. When combined with drug discrimination data (surmountable antagonism of effects of SR141716 by Delta(9)-THC and AM1346 but not by methanandamide, i.e. AM356), these data indicate that the anandamide analog AM1346 may be more behaviorally similar to cannabinoids like Delta(9)-THC than to other anandamide-based molecules such as methanandamide.

Anxiolytic effects of lavender oil inhalation on open-field behaviour in rats

To establish a valid animal model of the effects of olfactory stimuli on anxiety, a series of experiments was conducted using rats in an open-field test. Throughout, effects of lavender oil were compared with the effects of chlordiazepoxide (CDP), as a reference anxiolytic with well-known effects on open-field behaviour. Rats were exposed to lavender oil (0.1-1.0 ml) for 30 min (Experiment 1) or 1h (Experiment 2) prior to open-field test and in the open field or injected with CDP (10 mg/kg i.p.). CDP had predicted effects on behaviour, and the higher doses of lavender oil had some effects on behaviour similar to those of CDP. In Experiment 3, various combinations of pre-exposure times and amounts of lavender oil were used. With sufficient exposure time and quantity of lavender the same effects were obtained as in Experiment 2. Experiment 4 demonstrated that these behavioural effects of lavender could be obtained following pre-exposure, even if no oil was present in the open-field test. In Experiments 2-4, lavender oil increased immobility. Together, these experiments suggest that lavender oil does have anxiolytic effects in the open field, but that a sedative effect can also occur at the highest doses.

Effects of diazepam and zolpidem on EEG beta frequencies are behavior-specific in rats

A pharmacological dissociation of the relation between electroencephalographic (EEG) activity and behavior has been described for the benzodiazepines. While a decrease in high frequency EEG activity is associated with a decrease in arousal in drug-free conditions, sedative benzodiazepines increase beta activity. Non-benzodiazepine GABA A receptor modulators can increase beta activity as well. To further study the relationship between rat behavior and EEG under GABA A receptor modulation, EEG effects of diazepam (2.5 mg/kg) and zolpidem (2.5 mg/kg) were studied during different behaviors. Both drugs modulate the GABA A receptor, albeit that zolpidem shows α 1 subunit selectivity while diazepam is non-selective. A detailed analysis of rat open field behavior was made with a distinction of 25 behavioral elements. The EEG was segmented according to each behavioral element and a corresponding power spectrum calculated. Both diazepam and zolpidem increased EEG beta frequencies, characteristic for the benzodiazepines. However, the beta and gamma increase was specific for active behavior and not for inactivity. Interestingly, diazepam and zolpidem seemed to amplify, rather than dissociate, the relation between behavior and the EEG. It is hypothesized that the large increase in beta-3/gamma activity caused by diazepam and zolpidem is a compensatory mechanism that allows for behavioral activation, despite pharmacologically induced sedation.

P2 receptor-mediated effects on the open field behaviour of rats in comparison with behavioural responses induced by the stimulation of dopamine D 2-like and by the blockade of ionotrophic glutamate receptors

The effects of the P2 receptor ligands 2-methylthio ATP (2-MeSATP; 10 pmol)—as a non-specific agonist—and pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS; 10 pmol)—as a non-selective antagonist—after bilateral intra-accumbens injection on the locomotor response were investigated in an open field situation. The P2 receptor-mediated effects on the pattern of locomotor activity were compared with the effects caused by the dopamine D 2-like receptor agonist quinpirole (10 pmol) and by the combination of the N-methyl- d-aspartate (NMDA) receptor antagonist (±)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 10 pmol) with the α-amino-3-hydro-5-methyl-4-isoxazolpropionic acid (AMPA) and kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 30 pmol). The intra-accumbens injection of all tested compounds elicited an increase in the locomotor activity over a test period of 20 min when compared with the controls. No statistically significant differences could be evaluated between the different drug-treated groups. However, a more detailed analysis—using further behavioural parameters such as the number of movement direction changes, the effective running time and the running speed—revealed two basically different patterns of locomotor activity. The locomotor response induced by the injection of 2-MeSATP or quinpirole was characterised by a continuous and consistent locomotion, whereas the enhanced locomotor activity elicited by PPADS or CPP/CNQX was determined by an increased running speed accompanied by more disruptions and more changes of movement direction. The coadministration of 2-MeSATP and quinpirole led to an enhancement of locomotor activity in a limited post-treatment interval. The effects of both compounds could be abolished by the pre-treatment with the D 2/D 3 receptor antagonist sulpiride (100 pmol). Coadministration of PPADS and CPP/CNQX caused additive effects suggesting that the pathway mediated by P2 and ionotrophic glutamate receptors is different. The stimulation of P2 receptors in the nucleus accumbens (NAc) modulates the locomotion in the direction to be to be longer lasting, more consistent and more goal directed.

Fox odour affects corticosterone release but not hippocampal serotonin reuptake and open field behaviour in rats

Group-housed Sprague–Dawley (SD) rats exposed for 1 h to 2,5-dihydro-2,4,5-trimethylthiazoline (TMT, a component of fox feces) did not display changes in hippocampal serotonin (5-HT) metabolism and [ 3H]5-HT reuptake, compared to water or butyric acid. Such an observation extended to isolated SD and Fischer 344 rats. When group-housed SD rats were tested 1 week after a 1-h exposure to TMT, hippocampal 5-HT metabolism, [ 3H]5-HT reuptake, and [ 3H]paroxetine binding at the 5-HT transporter remained unchanged. This study questions TMT as a specific predatory stimulus as both butyric acid and TMT increased plasma corticosterone levels whilst leaving intact open field behaviour (at least in group-housed SD rats).

Physical and emotional stress have differential effects on preference for saccharine and open field behaviour in rats

Stress may influence the sensitivity of subjects to rewarding stimuli and stress modality may differentially affect this sensitivity. This relation was investigated in our animal model using chronic physical (repeated mild foot shocks) and emotional (witness) stress. Previous research has established that the two stressors have differential long-term effects on behaviour, where physical stress caused inactivity in a small open field and emotional stress hyperactivity. Rats were stressed on 5 consecutive days and tested for locomotor activity in a small open field (day 10) and saccharine preference (day 11). The preference for graded concentrations of saccharine over water was used as a measure for their sensitivity to reward. Physical stress treatment induced a long-term decrease both in preference for saccharine and open field activity compared to control treatment. Emotional stress animals showed an increase in open field behaviour activity and a slight increase in saccharine preference. Physical stress seems to cause anhedonia, while emotional stress might cause an increased sensitivity to reward. In conclusion, stress can induce differential long-term effects on sensitivity to positive stimuli and the response to novelty depending on stress modality.

Acute buspirone abolishes the expression of behavioral dopaminergic supersensitivity in mice.

Previous studies have shown that rats withdrawn from long-term treatment with dopamine receptor blockers exhibit dopaminergic supersensitivity, which can be behaviorally evaluated by enhanced general activity observed in an open-field. Recently, it has been reported that co-treatment with the non-benzodiazepine anxiolytic buspirone attenuates the development of haloperidol-induced dopaminergic supersensitivity measured by open-field behavior of rats. The aims of the present study were: 1) to determine, as previously reported for rats, if mice withdrawn from long-term neuroleptic treatment would also develop dopaminergic supersensitivity using open-field behavior as an experimental paradigm, and 2) to examine if acute buspirone administration would attenuate the expression of this behavioral dopaminergic supersensitivity. Withdrawal from long-term haloperidol treatment (2.5 mg/kg, once daily, for 20 days) induced a significant (30%) increase in ambulation frequency (i.e., number of squares crossed in 5-min observation sessions) but did not modify rearing frequency or immobility duration in 3-month-old EPM-M1 male mice observed in the open-field apparatus. Acute intraperitoneal injection of buspirone (3.0 and 10 but not 1.0 mg/kg, 12-13 animals per group) 30 min before open-field exposure abolished the increase in locomotion frequency induced by haloperidol withdrawal. These data suggest that the open-field behavior of mice can be used to detect dopaminergic supersensitivity, whose expression is abolished by acute buspirone administration.

Compulsive checking behavior of quinpirole-sensitized rats as an animal model of Obsessive-Compulsive Disorder(OCD): form and control

BackgroundA previous report showed that the open field behavior of rats sensitized to the dopamine agonist quinpirole satisfies 5 performance criteria for compulsive checking behavior. In an effort to extend the parallel between the drug-induced phenomenon and human obsessive-compulsive disorder (OCD), the present study investigated whether the checking behavior of quinpirole rats is subject to interruption, which is an attribute characteristic of OCD compulsions. For this purpose, the rat's home-cage was placed into the open field at the beginning or the middle of a 2-hr test.ResultsIntroduction of the home-cage reduced checking behavior, as rats stayed inside the cage. After 40 min, checking resurfaced, as quinpirole rats exited the home-cage often. An unfamiliar cage had no such effects on quinpirole rats or saline controls.ConclusionsChecking behavior induced by quinpirole is not irrepressible but can be suspended. Results strengthen the quinpirole preparation as an animal model of OCD compulsive checking.

Sedative effects of the dopamine D1 receptor agonist A 68930 on rat open-field behavior

The present results demonstrate sedative effects of the DA D1 receptor agonist A 68930 (0.9-15 micromol kg(-1), s.c.) on rat spontaneous locomotor activity in an open field. The effects were particularly strong, and dose-dependent, for the ambulatory activity in the open-field arena (forward locomotion) and for rearing activity, whereas the suppression of locomotor activity (i.e. total horizontal activity in the open field) was less conspicuous. The distribution of activity within the open field (activity in center vs periphery) was not consistently affected by the A 68930 treatment. In support for DA D1 receptor mediated effects of A 68930, the effects on locomotor activity, forward locomotion, and on rearing behavior, were partially antagonized by the DA D1 receptor antagonist SCH 23390 (15 nmol kg(-1) s.c.). SCH 23390 by itself produced a modest, but statistically significant, suppression of these different items of open-field behavior. The atypical antipsychotic agent clozapine has previously, in this laboratory, been shown to stimulate DA D1 receptors in vivo. There are a number of clinical and laboratory observations, consistent with the notion of a beneficial role for such effects in schizophrenia. Thus, the sedation, apparently not related to extrapyramidal motor functions, produced by DA D1 receptor agonist A 68930 could reflect an important aspect of the mechanism of action for atypical antipsychotic drugs.