Rats In Open Field Test 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.

Age-Associated Changes in Exploratory Activity in the Open Field Test in Rats Surviving Prenatal Hypoxia

Age-Associated Changes in Exploratory Activity in the Open Field Test in Rats Surviving Prenatal Hypoxia

Spinal cord stimulation reduces cardiac pain through microglial deactivation in rats with chronic myocardial ischemia.

Angina pectoris is cardiac pain that is a common clinical symptom often resulting from myocardial ischemia. Spinal cord stimulation (SCS) is effective in treating refractory angina pectoris, but its underlying mechanisms have not been fully elucidated. The spinal dorsal horn is the first region of the central nervous system that receives nociceptive information; it is also the target of SCS. In the spinal cord, glial (astrocytes and microglia) activation is involved in the initiation and persistence of chronic pain. Thus, the present study investigated the possible cardiac pain-relieving effects of SCS on spinal dorsal horn glia in chronic myocardial ischemia (CMI). CMI was established by left anterior descending artery ligation surgery, which induced significant spontaneous/ongoing cardiac pain behaviors, as measured using the open field test in rats. SCS effectively improved such behaviors as shown by open field and conditioned place preference tests in CMI model rats. SCS suppressed CMI-induced spinal dorsal horn microglial activation, with downregulation of ionized calcium-binding adaptor protein-1 expression. Moreover, SCS inhibited CMI-induced spinal expression of phosphorylated-p38 MAPK, which was specifically colocalized with the spinal dorsal horn microglia rather than astrocytes and neurons. Furthermore, SCS could depress spinal neuroinflammation by suppressing CMI-induced IL-1β and TNF-α release. Intrathecal administration of minocycline, a microglial inhibitor, alleviated the cardiac pain behaviors in CMI model rats. In addition, the injection of fractalkine (microglia-activating factor) partially reversed the SCS-produced analgesic effects on CMI-induced cardiac pain. These results indicated that the therapeutic mechanism of SCS on CMI may occur partially through the inhibition of spinal microglial p38 MAPK pathway activation. The present study identified a novel mechanism underlying the SCS-produced analgesic effects on chronic cardiac pain.

Effects of neuropeptides on behavior of rats in open field test and experimentally induced social stress

Effects of neuropeptides on behavior of rats in open field test and experimentally induced social stress

A novel rat robot controlled by electrical stimulation of the nigrostriatal pathway.

Artificial manipulation of animal movement could offer interesting advantages and potential applications using the animal's inherited superior sensation and mobility. Although several behavior control models have been introduced, they generally epitomize virtual reward-based training models. In this model, rats are trained multiple times so they can recall the relationship between cues and rewards. It is well known that activation of one side of the nigrostriatal pathway (NSP) in the rat induces immediate turning toward the contralateral side. However, this NSP stimulation-induced directional movement has not been used for the purpose of animal-robot navigation. In this study, the authors aimed to electrically stimulate the NSP of conscious rats to build a command-prompt rat robot. Repetitive NSP stimulation at 1-second intervals was applied via implanted electrodes to induce immediate contraversive turning movements in 7 rats in open field tests in the absence of any sensory cues or rewards. The rats were manipulated to navigate from the start arm to a target zone in either the left or right arm of a T-maze. A leftward trial was followed by a rightward trial, and each rat completed a total of 10 trials. In the control group, 7 rats were tested in the same way without NSP stimulation. The time taken to navigate the maze was compared between experimental and control groups. All rats in the experimental group successfully reached the target area for all 70 trials in a short period of time with a short interstimulus interval (< 0.7 seconds), but only 41% of rats in the control group reached the target area and required a longer period of time to do so. The experimental group made correct directional turning movements at the intersection zone of the T-maze, taking significantly less time than the control group. No significant difference in navigation duration for the forward movements on the start and goal arms was observed between the two groups. However, the experimental group showed quick and accurate movement at the intersection zone, which made the difference in the success rate and elapsed time of tasks. The results of this study clearly indicate that a rat-robot model based on NSP stimulation can be a practical alternative to previously reported models controlled by virtual sensory cues and rewards.

Metformin produces anxiolytic-like effects in rats by facilitating GABAA receptor trafficking to membrane.

Altered function or expression of GABAA receptors contributes to anxiety disorders. Benzodiazepines are widely prescribed for the treatment of anxiety. However, the long-term use of benzodiazepines increases the risk of developing drug dependence and tolerance. Thus, it is urgent to explore new therapeutic approaches. Metformin is widely used to treat Type 2 diabetes and other metabolic syndromes. However, the role of metformin in psychiatric disorders, especially anxiety, remains largely unknown. We examined the effects of metformin on anxiety-like behaviour of rats in open field test and elevated plus maze test. We also observed the effect of metformin (10μM, in vitro; 100mg·kg-1 , in vivo) on the trafficking of GABAA receptors, as mechanisms underlying the anxiolytic effects of metformin. Metformin (100mg·kg-1 , i.p. 30min) displayed a robust and rapid anxiolytic effect, without tolerance. Metformin up-regulated the surface expression of GABAA receptors and increased miniature inhibitory postsynaptic currents (mIPSCs). AMP-activated protein kinase (AMPK) activated by metformin-induced stimulation of forkhead box O3a (FoxO3a) transcriptional activity, followed by increased expression of GABAA receptor-associated protein (GABARAP) and its binding to GABAA receptors finally resulted in the membrane insertion of GABAA receptors. Metformin increased mIPSCs by up-regulating the membrane insertion of GABAA receptors, via a pathway involving AMPK, FoxO3a, and the GABAA receptor-associated protein. Thus metformin has a potential new use in the treatment of anxiety disorders.

Foshouningshen decoction improves sleeping via the serotonergic system in a rat model of insomnia

To evaluate the sedative and hypnotic effects of Foshouningshen decoction (FSNSD) and study its effects on expressions of 5-hydroxy tryptamine (5-HT) and 5-HT1A receptor (5-HT1AR) in the hippocampus in a rat model of insomnia. Male KM mice were divided into control group, estazolam (0.4 mg/kg daily) group, and low-, moderate-, and high-dose FSNSD groups (daily dose of 12, 24, and 48 g/kg, respectively). After corresponding treatments for 1 week, the mice underwent sleep-inducing test with subthreshold and threshold doses of sodium pentobarbital. Forty-eight male SD rats were randomized into control group, insomnia model group, estazolam group (0.2 mg/kg daily), and low-, moderate-, and high-dose FSNSD groups (with daily dose of 6, 12, and 24 g/kg, respectively). Rat models of insomnia were established by intraperitoneal injection of 4-cholro-dl-phenylalanine (PCPA) at the daily dose of 350 mg/kg for 3 days, after which the rats received corresponding treatments via gavage for 1 week. The performance of the rats in open field test was recorded and the hippocampal expression of 5-HT was detected using ELISA; the expressions of 5-HT1AR protein and mRNA in the hippocampus were detected using immunohistochemistry and real-time PCR, respectively. In the sleep-inducing test with a subthreshold dose of sodium pentobarbital, the mice treated with high-dose FSNSD showed a significantly higher rate of sleep onset than the control mice (P<0.05); in the test with a threshold dose of sodium pentobarbital, treatment with moderate- and high-dose FSNSD resulted in significantly prolonged sleeping time (P<0.01) and shortened sleep latency (P<0.05) in the mice. The rats in insomnia model group showed increased total distance in open field test (P<0.05) with significantly decreased content of 5-HT (P<0.01) and expressions of 5-HT1AR protein and mRNA in the hippocampus (P<0.01). Treatment of the rats with estazolam or high-dose FSNSD obviously decreased the total distance in open field test (P<0.05) and increased the content of 5-HT (P<0.05) and expressions of 5-HT1AR (P<0.01) in the hippocampus of rats with insomnia. FSNSD can produce therapeutic effects on insomnia possibly by increasing 5-HT content and expressions of 5-HT1AR in the hippocampus.

Early deprivation increases high-leaning behavior, a novel anxiety-like behavior, in the open field test in rats

The open field test is one of the most popular ethological tests to assess anxiety-like behavior in rodents. In the present study, we examined the effect of early deprivation (ED), a model of early life stress, on anxiety-like behavior in rats. In ED animals, we failed to find significant changes in the time spent in the center or thigmotaxis area of the open field, the common indexes of anxiety-like behavior. However, we found a significant increase in high-leaning behavior in which animals lean against the wall standing on their hindlimbs while touching the wall with their forepaws at a high position. The high-leaning behavior was decreased by treatment with an anxiolytic, diazepam, and it was increased under intense illumination as observed in the center activity. In addition, we compared the high-leaning behavior and center activity under various illumination intensities and found that the high-leaning behavior is more sensitive to illumination intensity than the center activity in the particular illumination range. These results suggest that the high-leaning behavior is a novel anxiety-like behavior in the open field test that can complement the center activity to assess the anxiety state of rats.

Impaired Interoception in a Preclinical Model of Functional Dyspepsia

IntroductionThe etiologies of functional dyspepsia symptoms, including postprandial distress syndrome, remain unknown. We tested the hypothesis that neonatal colon inflammation induces postprandial distress syndrome-like symptoms in adult life that associate with increased activation of vagal afferent pathways and forebrain limbic regions.ResultsThese rats showed a significant decrease in nutrient meal consumption to satiety after an overnight fast, decrease in gastric emptying, decrease in total distance traveled, and decrease in percent distance traveled in midfield versus control rats in open field test, indicating postprandial anxiety- and depression-like behaviors. Adult naïve rats treated with oral iodoacetamide to induce H. pylori-like mild gastritis demonstrated similar postprandial effects as the above rats.ConclusionsWe concluded that neonatal colon inflammation is a risk factor for the development of postprandial distress syndrome-like symptoms. While mild gastritis can induce symptoms similar to those of neonatal colon inflammation, gastritis in these rats does not worsen the symptoms.

Neurobehavioral effects of liraglutide and sitagliptin in experimental models

Glucagon-like peptide (GLP-1) receptor agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors are two currently approved therapies for type 2 diabetes mellitus (T2DM). Present study evaluated the effect of liraglutide (a long-acting GLP-1 agonist) and sitagliptin (a DPP-4 inhibitor) on nociception, anxiety, depression-like behavior and cognition in rats or mice.Nociception was assessed using tail-flick test; anxiety-behavior in open-field test and elevated plus maze (EPM) test while depression-like behavior was evaluated in forced swim test (FST) and tail-suspension test (TST). Cognition was assessed in EPM and Morris water maze (MWM) following memory deficit induced by pentylenetetrazole (PTZ) or scopolamine.In tail-flick test sitagliptin (6mg/kg) produced transient nociceptive effect. Liraglutide (200µg/kg) reduced peripheral square crossings by rats in open field test as well as reduced closed arm entries in the EPM, indicating a decline in exploratory behavior. In FST and TST models for depression, the duration of immobility with sitagliptin (6mg/kg) was reduced significantly in comparison to control group suggesting its antidepressant effect. Liraglutide did not show any antidepressant action. In EPM test for cognition, liraglutide and sitagliptin ameliorated the increase in transfer latency caused by PTZ in a dose-dependent manner. In MWM liraglutide and sitagliptin prevented the scopolamine-induced increase of the escape latency.This study shows that sitagliptin has mild antinociceptive effect and anti-depressant effect in the animal models of depression while liraglutide did not have such an effect. Liraglutide showed anxiogenic effects in the animal models. Both liraglutide and sitagliptin produced cognitive improvement in the animal models.

Comparison of Nootropic and Neuroprotective Features of Aryl-Substituted Analogs of Gamma-Aminobutyric Acid.

GABA analogs containing phenyl (phenibut) or para-chlorophenyl (baclofen) substituents demonstrated nootropic activity in a dose of 20 mg/kg: they improved passive avoidance conditioning, decelerated its natural extinction, and exerted antiamnestic effect on the models of amnesia provoked by scopolamine or electroshock. Tolyl-containing GABA analog (tolibut, 20 mg/kg) exhibited antiamnestic activity only on the model of electroshock-induced amnesia. Baclofen and, to a lesser extent, tolibut alleviated seizures provoked by electroshock, i.e. both agents exerted anticonvulsant effect. All examined GABA aryl derivatives demonstrated neuroprotective properties on the maximum electroshock model: they shortened the duration of coma and shortened the period of spontaneous motor activity recovery. In addition, these agents decreased the severity of passive avoidance amnesia and behavioral deficit in the open field test in rats exposed to electroshock. The greatest neuroprotective properties were exhibited by phenyl-containing GABA analog phenibut.

Activation of KCNQ channels located on the skeletal muscle membrane by retigabine and its influence on the maximal muscle force in rat muscle strips.

Retigabine is a new antiepileptic drug with the main mechanism of action: activation of voltage-gated potassium channels (Kv7) represented in many tissues including the excitable cells-neuronal and muscular. The aim of this article is to determine the role of potassium channels located on the skeletal muscle membrane in the in vivo and in vitro reduction of muscle contractile activity induced by retigabine. We studied the effects of retigabine on the motor function in vivo using a bar holding test and exploratory activity using open field test in rats. Electrical field stimulation (EFS) was applied to skeletal muscle strips in vitro in order to evaluate muscular activity. We registered a significant decrease in the muscle tone and exploratory activity of rats, treated orally with 60mg/kg bw retigabine. In vitro experiments showed decrease in the maximal muscle force of strips in the presence of retigabine in the medium after both indirect (nerve-like) and direct (muscle-like) stimulation. The effects were fully antagonized by XE-991 (Kv7 channel blocker), which supports our hypothesis about the relation between these types of potassium channels and the observed change in the muscle force. Based on these results, we can conclude that skeletal muscle Kv7 channels play a significant role in the myorelaxation and reduced muscle force registered after treatment with Kv7 channels openers (e.g., retigabine). The hyperpolarization of skeletal muscle membrane caused by accelerated K(+) efflux may be the underlying cause for the effect of retigabine on the muscle tone.

The different effects of maternal separation on spatial learning and reversal learning in rats

Early postnatal maternal separation (MS) can play an important role in the development of psychopathologies during ontogeny. In the present study, we investigated the effects of repeated MS (4h per day from postnatal day (PND) 1 to 21) on locomotor activity and anxiety behavior in open field, spatial learning and reversal learning in Morris water maze of male and female juvenile (PND 21), adolescent (PND 35) and early adult (PND 56) Wistar rats. The results indicated that MS increased locomotor activity of rats across all ages and reduced anxiety behavior of adolescent rats in open field test. MS also increased swim distance in spatial learning and decreased escape latency in reversal learning in adolescent and early adult rats. Additionally, for socially reared rats, there was increased spontaneous locomotion with age, decreased reversal learning ability with age. The present study provides novel insights into the consequences of MS and demonstrates unique age-dependent changes at the behavioral levels.

Psychopharmacological studies of Mammea africana stem bark extract

Herbal medicine is an integral part of the health care system in most developed and developing countries of the world. Objective: The stem bark of Mammea africana used traditionally in the treatment of mental disorders was evaluated for depressive effect on the central nervous system (CNS). Materials and Method: The stem bark extract was investigated for depressive activity in the open field, force swimming and tail suspension tests as well as its anticonvulsant potential against pentylene tetrazol and aminophylline-induced convulsions. The effect of the extract on phenobarbitone induced sleeping time was also evaluated. Results: The extract was found to significantly (p&lt;0.001) decrease the frequency of line crossing, rearing and walling activities of the rats in open field test as well as increased the immobility time in both tail suspension and force swimming tests. The stem bark extract also significantly (p&lt;0.001) shortened the onset time of sleep and prolonged the duration of sleep induced by phenobarbitone sodium. The stem bark extract and fractions (30 – 90 mg/kg), could not offered significant protection against PTZand aminophylline induced convulsion, but were found to delay significantly (p&lt;0.05 – 0.001) the onset of tonic/clonic convulsion and also prolonged the time of death of the treated mice. Conclusion: The stem bark of M. africana has depressant, sedating and anticonvulsant properties.

Psychopharmacological studies of Mammea africana stem bark extract

Herbal medicine is an integral part of the health care system in most developed and developing countries of the world. Objective: The stem bark of Mammea africana used traditionally in the treatment of mental disorders was evaluated for depressive effect on the central nervous system (CNS). Materials and Method: The stem bark extract was investigated for depressive activity in the open field, force swimming and tail suspension tests as well as its anticonvulsant potential against pentylene tetrazol and aminophylline-induced convulsions. The effect of the extract on phenobarbitone induced sleeping time was also evaluated. Results: The extract was found to significantly (p&lt;0.001) decrease the frequency of line crossing, rearing and walling activities of the rats in open field test as well as increased the immobility time in both tail suspension and force swimming tests. The stem bark extract also significantly (p&lt;0.001) shortened the onset time of sleep and prolonged the duration of sleep induced by phenobarbitone sodium. The stem bark extract and fractions (30 – 90 mg/kg), could not offered significant protection against PTZand aminophylline induced convulsion, but were found to delay significantly (p&lt;0.05 – 0.001) the onset of tonic/clonic convulsion and also prolonged the time of death of the treated mice. Conclusion: The stem bark of M. africana has depressant, sedating and anticonvulsant properties.

Antidepressant and anti-anxiety like effects of 4i (N-(3-chloro-2-methylphenyl) quinoxalin-2-carboxamide), a novel 5-HT3 receptor antagonist in acute and chronic neurobehavioral rodent models

Depression and anxiety are the most debilitating mood disorders with poor therapeutic recovery rates. In the last decades, 5-HT3 receptor antagonists have been identified as potential agents for mood disorders. The current investigation focuses on evaluating the, antidepressant and anti-anxiety like effects of a novel 5-HT3 antagonist, 4i (N-(3-chloro-2-methylphenyl) quinoxalin-2-carboxamide). Preliminary, in vitro 5-HT3 receptor binding affinity was performed in isolated longitudinal muscle-myenteric plexus from the guinea pig ileum. Consequently, neurobehavioral effects of 4i in acute and chronic rodent models were evaluated. In addition, involvement of serotonergic system in the postulated effects of the compound was analyzed by in vivo assay. in vitro, 4i demonstrated high 5-HT3 receptor antagonistic activity (pA2, 7.6). in vivo acute study, 4i exhibited decreased duration of immobility in forced swim and tail suspension tests, and increased exploratory parameters as number and duration of nose-poking in hole board test and latency and time spent in aversive brightly illuminated light chamber in light–dark model. Moreover, in chronic model of depression, i.e., olfactory bulbectomy with behavioral deficits, 4i reversed depressive anhedonia in sucrose preference test and anxious hyperactive behavior in open field test in rats. Furthermore, synergistic effect of 4i with fluoxetine (a selective serotonin reuptake inhibitor) and inhibitory effect of 1-(m-chlorophenyl)-biguanide (a 5-HT3 receptor agonist) revealed serotonergic modulation by 4i mediated 5-HT3 receptor antagonism, which was further confirmed by potentiation of 5-hydroxytryptophan (a serotonin synthesis precursor) induced head twitch response. These findings suggest the potential antidepressant and anti-anxiety like effects of 4i, which may be related to the modulation of serotonergic system.

Effects of SCH-23390 in Combination with a Low Dose of 17β-Estradiol on Anxiety-Like Behavior in Ovariectomized Rats

The aim of this study was to explore effects on anxiety-like behavior of D1 dopamine receptor agonist, SKF-38393, and of D1 dopamine receptor antagonist, SCH-23390, given alone or in combination with a low dose of 17β-estradiol (17β-E2) to ovariectomized (OVX) rats. Two weeks after surgery, OVX rats began 14 days of treatment with the vehicle, a low dose of 17β-E2 (5.0 μg/rat, s.c.), SKF-38393 (0.1 mg/kg, i.p.), SCH-23390 (0.1 mg/kg, i.p.), SKF-38393 plus 17β-E2, or SCH-23390 plus 17β-E2. The animals were tested in the black and white model (BWM) and the open field test (OFT). SCH-23390 (0.1 mg/kg, i.p.) alone or in a combination with a low dose of 17β-E2 (5.0 μg/rat, s.c.) resulted in anxiolytic-like effect in OVX rats in the BWM. Repeated treatment with SCH-23390 and 17β-E2 profoundly increased anxiolytic-like effect of single substances exerted per se. Coadministration of SCH-23390 with 17β-E2 increased frequency of rearing and grooming in OVX rats in OFT. SKF-38393 (0.1 mg/kg, i.p.) treatment failed to alter anxiety-like behavior in OVX rats in the BWM. The results of the present study suggest that 17β-E2 and SCH-23390 interact to exert anxiolytic-like action and that each of these drugs can potentiate effects of each other.

Adjuvant effects of classical music on simvastatin induced reduction of anxiety but not object recognition memory in rats.

Simvastatin is one of many hydroxymethylglutaryl-coenzyme-A reductase inhibitors that are prescribed to lower cholesterol. Some emerging evidence indicates that classical music can serve as an effective adjuvant in rats treated with simvastatin. Moreover, simvastatin and classical music have been shown to influence some cognitive functions. To further understand the mechanisms of action, we exposed rats to classical music for 1 month, and then treated them orally with simvastatin. The behavioral experiments suggested that exposure to subchronic simvastatin (1 or 10 mg/kg/day) reduced anxiety levels in the elevated plus-maze and open-field test in rats exposed to Mozart music. The recognition object test results indicated that simvastatin altered non-spatial working memory only at the 1 mg/kg/day dose and improved both short- and long-term object recognition. No significant differences were found between Mozart music and silence in the object recognition test, suggesting that music did not significant affect learning and memory in adult rats. We hypothesize that the anxiolytic, but not object-recognition memory, effects of simvastatin and classical music occur through similar mechanisms, providing an important foundation for future preclinical and clinical research.

Acupuncture Activates ERK-CREB Pathway in Rats Exposed to Chronic Unpredictable Mild Stress

Extracellular signal-regulated kinase (ERK)-cAMP response element binding protein (CREB) signal pathway has been implicated in the pathogenesis of depression. There is growing evidence that acupuncture in traditional Chinese medicine has antidepressant-like effect. However, the effect of acupuncture on ERK-CREB pathway remains unknown. In our study, the antidepressant-like effect of acupuncture treatment was measured by sucrose intake test and open field test in rats exposed to chronic unpredictable mild stress (CUMS) for 4 weeks. The protein levels of ERK1/2, CREB, phosphorylated ERK1/2 (p-ERK1/2), and phosphorylated CREB (p-CREB) in the hippocampus (HP) and prefrontal cortex (PFC) were examined by Western blot analysis. Our results showed that CUMS rats exhibited the reduction in behavioral activities, whereas acupuncture stimulation at acupoints Baihui (Du20) and Neiguan (PC6) reversed the behavioral deficit. In addition, exposure to CUMS resulted in the decrease of p-ERK1/2 and p-CREB in the HP and PFC. Acupuncture increased the ratio of p-ERK1/2 to ERK1/2 and the ratio of p-CREB to CREB in the HP and PFC. Our study suggested that one potential way, by which acupuncture had antidepressant-like effect, might be mediated by activating the ERK-CREB pathway in the brain.

Effects of RFamide-Related Peptide (RFRP)-1 and RFRP-3 on Oxytocin Release and Anxiety-Related Behaviour in Rats

RFamide-related peptides (RFRP-1 and RFRP-3) are localised in neurones of the dorsomedial hypothalamus in rats. The dorsomedial hypothalamus plays an essential role in neuroendocrine and behavioural stress responses. In the present study, we examined the role of RFRP in the control of neuroendocrine and behavioural responses in rats. Stressful stimuli increased expression of Fos protein in RFRP-immunoreactive neurones of the dorsomedial hypothalamus, suggesting that stressful stimuli activate RFRP neurones. Intracerebroventricular injection of RFRPs increased the expression of Fos protein in oxytocin neurones in the hypothalamus and plasma concentrations of adrenocorticotrophic hormone and oxytocin. The hypothalamic paraventricular and supraoptic nuclei expressed mRNA of GPR147, the putative RFRP receptor, and application of RFRPs to isolated supraoptic nuclei facilitated oxytocin release, suggesting that RFRPs activate oxytocin neurones directly. Furthermore, the administration of RFRPs induced anxiety-related behaviour in rats in open-field tests. All these data taken together suggest that RFRPs play a role in the control of neuroendocrine and behavioural stress responses in rats.