Rats In Open Field Research Articles

Color-Coding Method Reveals Enhancement of Stereotypic Locomotion by Phenazepam in Rat Open Field Test

One of the most important tasks in neuroscience is the search for theoretical foundations for the development of methods for diagnosing and treating neurological pathology, and for assessing the effect of pharmacological drugs on the nervous system. Specific behavioral changes associated with exposure to systemic influences have been invisible to the human eye for a long time. A similar pattern of changes is characteristic of phenazepam, a drug with a wide range of effects on the brain. In this study, we used a color-coding method, which consists of combining three time positions in one image, the present (0 s), the near future (0.33 s) and the far future (1.6 s). This method made it possible to identify movement patterns, such as the initialization of ahead movements, side turns and 180° turns (back), and also to determine the degree of predictability of future movements. The obtained data revealed a decrease in the number of turns to the sides while maintaining ahead movement, as well as an increase in the predictability of movements in rats under the influence of phenazepam. Thus, sedative doses of phenazepam do not exhibit general depression of brain functions, but the inhibition of specific centers, including the medial prefrontal cortex and postsubiculum, which are involved in stereotypic locomotive behavior.

Genome-Wide Association Study on Three Behaviors Tested in an Open Field in Heterogeneous Stock Rats Identifies Multiple Loci Implicated in Psychiatric Disorders.

Many personality traits are influenced by genetic factors. Rodents models provide an efficient system for analyzing genetic contribution to these traits. Using 1,246 adolescent heterogeneous stock (HS) male and female rats, we conducted a genome-wide association study (GWAS) of behaviors measured in an open field, including locomotion, novel object interaction, and social interaction. We identified 30 genome-wide significant quantitative trait loci (QTL). Using multiple criteria, including the presence of high impact genomic variants and co-localization of cis-eQTL, we identified 17 candidate genes (Adarb2, Ankrd26, Cacna1c, Cacng4, Clock, Ctu2, Cyp26b1, Dnah9, Gda, Grxcr1, Eva1a, Fam114a1, Kcnj9, Mlf2, Rab27b, Sec11a, and Ube2h) for these traits. Many of these genes have been implicated by human GWAS of various psychiatric or drug abuse related traits. In addition, there are other candidate genes that likely represent novel findings that can be the catalyst for future molecular and genetic insights into human psychiatric diseases. Together, these findings provide strong support for the use of the HS population to study psychiatric disorders.

Gender differences in anxiety response to high intensity white noise in rats

Prolong exposure to high intensity white noise (HIWN), defined as a heterogeneous mixture of sound waves extending over a wide frequency range, has detrimental peripheral and central consequences including cardiovascular and emotional effects. Anxiety is a common manifestation of HIWN. Although gender-dependent differences in manifestation of anxiety and/or response to treatment of this condition has been amply documented, potential differences in response to HIWN, a common exposure in combat, construction and rave disco, has not been adequately investigated. In this study, both male and female Wistar rats were subjected to HIWN for 10 consecutive days, 1 h/day. On day 11, a day after the last exposure, the performance of the rats in open field (OF) and elevated plus maze (EPM) was evaluated. Male rats showed a higher anxiety-like response to HIWN as evidenced by: lower number of entries into the open arm of the EPM, lower number of entries into central zone of OF, excess grooming in OF and more boluses in closed arm of EPM. These results indicate that gender-related differences in anxiety in general, and in response to HIWN, in particular, has to be taken into consideration when investigating the neurobiological components and/or treatment modalities.

Short-Term Alterations in Behavior and Astroglial Function After Intracerebroventricular Infusion of Methylglyoxal in Rats.

Methylglyoxal (MG) is a by-product of glycolysis. In pathological conditions, particularly diabetes mellitus, this molecule is unbalanced, causing widespread protein glycation. In addition to protein glycation, other effects resulting from high levels of MG in the central nervous system may involve the direct modulation of GABAergic and glutamatergic neurotransmission, with evidence suggesting that the effects of MG may be related to behavioral changes and glial dysfunction. In order to evaluate the direct influence of MG on behavioral and biochemical parameters, we used a high intracerebroventricular final concentration (3μM/μL) to assess acute effects on memory and locomotor behavior in rats, as well as the underlying alterations in glutamatergic and astroglial parameters. MG induced, 12h after injection, a decrease in locomotor activity in the Open field and anxiolytic effects in rats submitted to elevated plus-maze. Subsequently, 36h after surgery, MG injection also induced cognitive impairment in both short and long-term memory, as evaluated by novel object recognition task, and in short-term spatial memory, as evaluated by the Y-maze test. In addition, hippocampal glutamate uptake decreased and glutamine synthetase activity and glutathione levels diminished during seventy-two hours after infusion of MG. Interestingly, the astrocytic protein, S100B, was increased in the cerebrospinal fluid, accompanied by decreased hippocampal S100B mRNA expression, without any change in protein content. Taken together, these results may improve our understanding of how this product of glucose metabolism can induce the brain dysfunction observed in diabetic patients, as well as in other neurodegenerative conditions, and further defines the role of astrocytes in disease and therapeutics.

Interactions of the estrous cycle, novelty, and light on female and male rat open field locomotor and anxiety-related behaviors

Animal behavior can be modulated by multiple interacting factors. In rodents such as rats, these factors include, among others, the female estrous cycle, exposure to a novel environment, and light. Here, we used the open field test to disassociate differences in behavior resulting from each of these factors by testing the hypothesis that locomotor and anxiety-related behaviors differ between estrous cycle phases in female rats and that novelty and light exposure concurrently influence these behaviors in both female and male rats. Adult female rats were tested twice under red or white light in estrus and diestrus estrous cycle phases. Adult male rats were also tested twice under either red or white light. In females, an interaction between novelty and estrous cycle phase influenced locomotor and anxiety-related behaviors. In males, novelty influenced locomotor and anxiety-related behaviors differentially under red and white light. Light exposure increased anxiety-related behaviors in both males and females, but reduced locomotor behavior only in females. These findings reveal the complexities of behavioral testing and highlight the importance of factors such as the estrous cycle, novelty, and light exposure.

The effects of PPAR-γ agonist pioglitazone on anxiety and depression-like behaviors in lipopolysaccharide injected rats

Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists have been suggested to have some effects of central nervous system. In the present study, the effects of PPAR-γ agonist pioglitazone (pio) on anxiety and depression-like behaviors were investigated in lipopolysaccharide (LPS) injected rats. The animal groups include (n = 10 in each): (1) control, (2) LPS (1 mg/kg, two hours before behavioral tests), (3–5) LPS + Pio 10, LPS + Pio 20, and LPS + Pio 30 groups which received 10, 20, and 30 mg/kg of pio respectively and 30 min later were injected by LPS. Pretreatment by pio improved the behaviors of the LPS injected rats in open field, elevated plus maze and forced swimming tests protected from brain tissues oxidative damage and reduced in total white blood cell (WBC). It was indicated that pio had anti-anxiety and anti-depressant effect in LPS injected rats.

Social and anxiety-like behaviors contribute to nicotine self-administration in adolescent outbred rats

Both emotional and social traits interact with genetic factors to influence smoking behavior. We previously established a socially acquired nicotine intravenous self-administration model where social learning of a nicotine-associated odor cue reversed conditioned flavor aversion and promoted nicotine intake. In this study, we first phenotyped ~800 adolescent heterogeneous stock rats in open field, novel object interaction, social interaction, elevated plus maze, and marble burying behaviors. These rats were then phenotyped on socially acquired nicotine self-administration. We found 243 significant correlations between different behavioral tests. Principal component regression analysis found that ~10–20% of the variance in nicotine-related measures, such as intake during the first or the last three fixed-ratio sessions, the progressive ratio session, and reinstatement behavior, can be explained by variations in behavioral traits. Factors corresponding to social behavior and anxiety were among the strongest predictors of nicotine intake and reinstatement of nicotine-seeking behavior. We also found many sex differences in behavioral measures. These data indicated that the genetic diversity of this population, in combination with social behaviour and anxiety, are significant contributors to the divergent nicotine self-administration behavior and indicated a high probability of discovering sex-specific genetic mechanisms for nicotine intake in future genome-wide association studies.

Effects of noradrenergic and serotonergic systems on risk-based decision-making and center arena activity in open field in rats

Center arena activity in open field (OF) test is associated with risk-taking behaviors. Noradrenaline and serotonin (5-HT) are neurotransmitters involved in both center arena activity and risk-based decision-making. However, the effects of noradrenergic/serotonergic systems on risk-based decision-making in rats with different center arena activity levels have not been clearly characterized. In this study, we explored the effects of the noradrenergic and serotonergic systems on risk-based decision-making in long center-time (LCT group) and short center-time (SCT group) rats. The two groups were formed based on performance in OF test. Then we tested their risk-based decision-making using probability discounting task (PDT); rats had to choose between “small/certain” lever that always delivered one pellet and “large/risky” lever that delivered four pellets in a probabilistic manner (100%, 50%, 25%, 12.5%). The results showed the SCT group chose the large/risky lever less often in 12.5% block and were more sensitive to loss than the SCT group. α2-adrenergic receptor agonist dexmedetomidine (0.01 mg/kg) decreased the frequency of risky choice, while the noradrenaline reuptake inhibitor (NRI) reboxetine (10 mg/kg) had the opposite effect only in the SCT group. Serotonin-noradrenaline reuptake inhibitor (SNRI) duloxetine (5 mg/kg) decreased preference for the large/risky option only in the SCT group. In contrast, pharmacological manipulations of the serotonin system did not affect the frequency of risky choices. These results suggest that noradrenergic system may be involved in weighing gains and losses for probabilistic discounting. Our findings also provide a better understanding of the involvement of center arena activity in risk-taking.

Acute food deprivation separates motor-activating from anxiolytic effects of caffeine in a rat open field test model.

Similar doses of caffeine have been shown to produce either anxiolytic or anxiogenic effects in rats. The reasons for these conflicting results are not known. We hypothesized that food deprivation stress interacts with the stimulant effects of caffeine to increase anxiety-like behavior. We tested 32 female Sprague Dawley rats in a dim open field for 10 min. Half of the animals were food deprived for 24 h and injected (intraperitoneal) with caffeine (30 mg/kg; n=7) or deionized water (n=8) 20 min before the open field test. The other half was nondeprived and injected with caffeine (30 mg/kg; n=8) or deionized water (n=9). Results showed that nondeprived rats injected with caffeine moved longer distances and at a greater speed in the periphery and moved longer distances and spent more time in the center than rats treated with vehicle, indicative of motor-activating and/or anxiolytic effects of caffeine. Rats that were food deprived and injected with caffeine moved longer distances in the center and tended to spend more time there, indicative of anxiolysis. We conclude that caffeine had two effects on behavior, motor activation and a reduction of anxiety, and that food deprivation separated these effects.

Nutritional Treatment of Anaemia as Compare to Marketed Available Drug (Ferrous Sulfate) in Animal Model

Aim: To study the nutritional treatment of anaemia as compare to marketed available drug (Ferrous sulfate) in animal model.Methodology: Total 24 rats were included in the study, divided into 4 groups. Control group was treated with saline. Anaemia was produced in model and both test groups by pricking on their tail and drawn 2-3 drops of blood daily for one week. After producing anaemia model remained same and test group 1 were treated with the marketed available anti-anaemic drug called Ferrous sulphate of 30 mg/kg body weight and test group 2 treated with natural anti-anaemic Illicium verum extract of 80 mg/kg body weight for 6 weeks respectively.Result: Illicium verum extract increases locomotor activity in T2 rats therefore; rats open field activity was increased. It decreases depression and long-term memory but enhanced short term memory. It also produces anxiolytic effect as compare to ferrous sulfate. Haematological study including RBC, PCV, MCHC and platelets were shown significantly increased in T2 group of rats while lymphocyte, MCH and MCV were decreased.Conclusion: It was concluded in the study that the Illicium verum extract produce same effect as common medicine ferrous sulfate on rat’s model. In developing country, such as Pakistan the rate of anaemia was increased so there is a need of finding natural compounds to cure anaemia. Natural remedies were vital in modern era because natural compound do not produce side effect.

Antidepressant effects of standardized extract of Centella asiatica L in olfactory bulbectomy model

Centella asiatica Linn leaves extract are reported to have promising antidepressant activity in acute animal models of depression. The aim of the present study is to evaluate the effects of standardized extract of Centella asiatica L leaves (INDCA) in rats using chronic stress medicated depression model in rats i.e. olfactory bulbectomy model. INDCA was extracted from Centella asiatica L. leaves and standardized to its bioactive constituent, asiaticoside, by HPLC. Effects of 14-day (subacute) oral pretreatment of INDCA (3, 10, or 30mg/kg), imipramine (20mg/kg), fluoxetine (30mg/kg) and desipramine (15mg/kg) were evaluated after behavioral depression induced by olfactory bulbectomy (OBX) in rats. Separate sham and vehicle control groups were also maintained. Food intake and body weight were measured 1h prior to treatment (day 1, baseline), and on 7th day and 14th day of treatment. Behavioral and physiological parameters in open field and elevated plus maze were recorded on 14th day of treatment. Dose-dependent reversal of reduction of body weight, body temperature, and heart rate with the normalization of elevated food intake that was observed in OBX rats treated with INDCA. Hyperactivity shown by OBX rats in open field and elevated plus maze paradigm was significantly reversed by INDCA. In conclusion, INDCA exerts antidepressant effects in OBX model in rats.

Male Hatano High-Avoidance Rats Show High Avoidance and High Anxiety-Like Behaviors as Compared with Male Low-Avoidance Rats

Our prime objective was to establish an optimal model animal for studying avoidance learning and memory in rodents. The two-way rat inbred strains of Hatano high- (HAA) and low-avoidance (LAA) animals were originally selected and bred in accordance with their high or low performance respectively in the shuttle-box active avoidance task. Previous studies demonstrated that they have clear strain differences in endocrine stress response, which is related to acquisition of aversive learning and emotional reactivity. To evaluate the effect of selection by the shuttle-box task on avoidance performance and emotional reactivity, male Hatano rats underwent passive avoidance, open field and elevated plus maze tests. The present results show that the avoidance performance in the passive task was significantly greater in HAA rats than in LAA rats. Furthermore, HAA rats showed high anxiety-like behaviors compared with LAA rats in open field and elevated plus maze tests. Taken together, this study demonstrated that 1) selection and breeding of Hatano HAA and LAA strain rats by shuttle-box task had been properly carried out with the criterion of high and low avoidance performance respectively and that 2) HAA rats were predisposed to high anxiety compared with LAA rats. These results indicated that Hatano HAA and LAA rats can be useful models for studying avoidance learning and memory.

Emotional reactivity and cognitive performance in aversively motivated tasks: a comparison between four rat strains.

BackgroundCognitive function might be affected by the subjects' emotional reactivity. We assessed whether behavior in different tests of emotional reactivity is correlated with performance in aversively motivated learning tasks, using four strains of rats generally considered to have a different emotional reactivity.MethodsThe performance of male Brown Norway, Lewis, Fischer 344, and Wistar Kyoto rats in open field (OF), elevated plus-maze (EPM), and circular light-dark preference box (cLDB) tasks, which are believed to provide measures of emotional reactivity, was evaluated. Spatial working and reference memory were assessed in two aversively motivated learning and memory tasks: the standard and the "repeated acquisition" versions of the Morris water maze escape task, respectively. All rats were also tested in a passive avoidance task. At the end of the study, levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid, and 5-HT turnover in the hippocampus and frontal cortex were determined.ResultsStrain differences showed a complex pattern across behavioral tests and serotonergic measures. Fischer 344 rats had the poorest performance in both versions of the Morris water escape task, whereas Brown Norway rats performed these tasks very well but the passive avoidance task poorly. Neither correlation analysis nor principal component analysis provided convincing support for the notion that OF, EPM, and cLDB tasks measure the same underlying trait.ConclusionsOur findings do not support the hypothesis that the level of emotional reactivity modulates cognitive performance in aversively motivated tasks. Concepts such as "emotional reactivity" and "learning and memory" cannot adequately be tapped with only one behavioral test. Our results emphasize the need for multiple testing.

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.

Role of 5-HT 1A receptors in the mediation of acute citalopram effects : A 8-OH-DPAT challenge study

(1) The study was aimed to investigate the effects of the minimal effective doses of acute citalopram (5 mg/kg), (±)-8-hydroxy-dipropylaminotetralin HBr (8-OH-DPAT; 0.1 mg/kg), and their combined treatment on the rat open field and forced swimming behaviour and post-mortem monoamine content. (2) The animals were prospectively divided into the vehicle- and para-chlorophenylalanine ( p-CPA)-pretreated (350 mg/kg) groups. (3) Acute citalopram (5 mg/kg), 8-OH-DPAT (0.1 mg/kg), or their combined treatment had no major effect on the rat open field and forced swimming behaviour. (4) The post-mortem catecholamine content in four brain regions studied was unchanged in all treatment groups. (5) The combined 8-OH-DPAT (0.1 mg/kg) and citalopram (5 mg/kg) treatment partially reversed the p-CPA-induced decrease of serotonin (5-HT) and 5-hydroxy-indolacetic acid (5-HIAA) content. (6) The present experiments demonstrate that the 5-HT 1A receptors mediate some of the selective serotonin reuptake inhibitor (SSRI)-induced biochemical phenomena.

Social attraction between rats in open field: long-term consequences of kindled seizures

Kindling of the amygdaloid complex in rats results in an enhanced emotionality frequently expressed by an elevated anxiety and defensive attitude toward other animals. Defensive attitude may have important consequences in social context and if tested in a large space it may eventually lead to social withdrawal. To test this hypothesis, rats were subjected to daily kindling sessions and their behavior was compared to implanted-sham and intact rats. Blood was collected after selected kindling trials for assessment of corticosterone response. Behavioral tests started 1 month after the last kindling trial and consisted of two open field sessions. A solitary rat was tested in the 1st session and pair of rats was tested simultaneously in the second session. Results showed that kindling changed the balance between exploration and occupation of a home base (HB) in the open field, in favor of higher preference of the home base occupancy. These results were apparent only during the social session leading to the conclusion that rats preferred to stay in the home base to maximize the proximity to a partner rat. This was supported by the observation that by increasing the occupancy of the HB, the kindled rats accomplished the longest concurrent presence with the partner rat in the common HB. We discuss the level of inter-rats aggression as a factor defining whether the anxious kindled rats will respond with increased or decreased social attraction in the open field test.

The effects of dopamine D2 receptor ligands on novelty‐induced behavior in the rat open field test

To determine the potential role of dopamine D2 receptor in mechanisms of anxiety, the effects of the preferential dopamine D2 receptor agonist, quinpirole, and antagonists, haloperidol and (–) sulpiride, were examined, in comparison to the action of the preferential dopamine D3 receptor agonist, (±)7-OH-DPAT and d-amphetamine, in the rat open field test. The effects of dopamine D2 receptor ligands in active doses were additionally verified in the Vogel conflict procedure. Quinpirole at the lower dose of 1.0 mg/kg produced a selective anti-thigmotactic effect, and increased the number of entries into the central part of the open field, without any influence on animals motility. At this dose the drug also increased punished but not free drinking. Both haloperidol and (–) sulpiride reduced the number of entries into the central sector of the open field without changing rat motor activity. (–) Sulpiride in a dose-dependent manner decreased also the time spent in the central part of the open field. No effect of the antipsychotics was observed in the Vogel conflict test. (±)7-OH-DPAT failed to exert any action in the open field test, except the general inhibitory effect at the highest dose examined. d-Amphetamine increased rats ambulation without any effect on exploratory behavior. The data are discussed in relation to the role of changes in dopaminergic activity in modulation of anxiety, and relative importance of dopamine D2 receptor mechanisms.

The effects of dopamine D2 receptor ligands on novelty-induced behavior in the rat open field test

To determine the potential role of dopamine D2 receptor in mechanisms of anxiety, the effects of the preferential dopamine D2 receptor agonist, quinpirole, and antagonists, haloperidol and (–) sulpiride, were examined, in comparison to the action of the preferential dopamine D3 receptor agonist, (±)7-OH-DPAT and d-amphetamine, in the rat open field test. The effects of dopamine D2 receptor ligands in active doses were additionally verified in the Vogel conflict procedure. Quinpirole at the lower dose of 1.0 mg/kg produced a selective anti-thigmotactic effect, and increased the number of entries into the central part of the open field, without any influence on animals motility. At this dose the drug also increased punished but not free drinking. Both haloperidol and (–) sulpiride reduced the number of entries into the central sector of the open field without changing rat motor activity. (–) Sulpiride in a dose-dependent manner decreased also the time spent in the central part of the open field. No effect of the antipsychotics was observed in the Vogel conflict test. (±)7-OH-DPAT failed to exert any action in the open field test, except the general inhibitory effect at the highest dose examined. d-Amphetamine increased rats ambulation without any effect on exploratory behavior. The data are discussed in relation to the role of changes in dopaminergic activity in modulation of anxiety, and relative importance of dopamine D2 receptor mechanisms.

Role of AVP in mediating the altered core temperature response to a simulated open field in pregnant rats.

Near the term of pregnancy, rats have an attenuated core temperature response on exposure to a novel environment (e.g., a simulated open field) compared with that observed early in pregnancy or in nonpregnant rats. The present experiments were carried out on 26 nonpregnant and 26 pregnant rats to test the hypothesis that arginine vasopressin, functioning as an endogenous antipyretic substance in the central nervous system, mediates this attenuated core temperature response. Exposure to a simulated open field after intracerebroventricular (ICV) vehicle produced a significant increase in core temperature in both nonpregnant and pregnant animals, the magnitude and duration of which were greater in the nonpregnant rats. In nonpregnant rats, exposure to a simulated open field after ICV vasopressin V(1)-receptor antagonist altered the pattern of the core temperature response but not the core temperature index compared with that observed on exposure to a simulated open field after ICV vehicle. In pregnant animals, ICV vasopressin V(1)-receptor antagonist did not alter the core temperature response to a simulated open field compared with that observed after ICV vehicle. Thus our data do not support the hypothesis that a pregnancy-related activation of arginine vasopressin attenuates the core temperature response to a simulated open field in rats near the term of pregnancy.

CGP 42112A abolishes facilitation of recognition caused by angiotensin II and angiotensin II(3-7) in rats.

The role of the angiotensin AT2 receptors in some behavioural effects of angiotensin II (Ang II) and its 3-7 fragment [Ang II(3-7)], using their selective antagonist CGP 42112A, was assessed. Ang II and Ang II(3-7), given intracerebroventricularly (icv) at the dose of 1 nmole each, substantially improved object recognition memory and enhanced apomorphine (1 mg/kg) stereotypy. Pre-treatment of rats with CGP 42112A (2 micrograms), per se ineffective in all tests, abolished activity of both peptides. None of the treatments significantly changed behaviour of rats in open field. The results point to the considerable involvement of the AT2 angiotensin receptors in the improvement of recognition memory caused by Ang II and Ang II(3-7).