Dark Exploration Test Research Articles

Evaluation of Anti-Anxiety Activity of Ethanolic Extract of Doronicum Hookeri Rhizome in Swiss Albino Mice

The Aim of this study is the “Evaluation of anti-anxiety activity of Ethanolic Extract of plant Doronicum Hookeri Rhizome in Swiss Albino Mice.” Methods: Twenty Swiss Albino Mice are of either sex selected with weight 20-30gm. Elevated Plus Maze and Light and Dark Exploration test was performed on them with full safety and hygiene. This consists of a 10cm x 10cm central platform, elevated 50cm off the ground, connected to two open arms 50x10cm and two closed arms 50cm x 40cm x 10cm. Swiss albino rats weighing 20-40 g were treated with OS extract, diazepam, and gum arabic for 30 min and then individually placed in the middle of an increasing number of arm diameters. Closing time is 5 minutes for both arms to open and close. Elapsed time is in seconds. The number of entries into the open and closed arms was counted during the test. Entry means that all four paws are on the arms. And in Light and Dark Exploration test: The installation consisted of two square boxes, each measuring 50 cm x 50 cm x 50 cm, separated by wooden walls. One of the boxes is dark and the other is illuminated by a 7W/12V lamp. There is an opening (6 cm x 6 cm) in the middle of the wooden wall that can be opened and closed using a transparent Plexiglas sliding door through which the animals can move from both sides. Mice were placed individually in the center of the light box and monitored for the next 5 min. Time spent in both boxes in seconds. The number of passes in the box is also indicated. Mice were treated with OS extract, diazepam, for 30 min before being placed in the light box. Result: Ethanolic extract of Doronicum Hookeri is found satisfactory, results show the increase in time spent in Open Maze and decreased in closed maze. Similarly time spent in Open Arena is increased as in closed arena. The value is calculated as Controlled, Standard, Low Dose and High Dose. Conclusion: The ethanolic extract showed significant anti-anxiety effect (p<0.04) when compared to control group.

Agarwood essential oil inhalation exerts antianxiety and antidepressant effects via the regulation of Glu/GABA system homeostasis.

Depression and anxiety are common diseases that endanger the physical and mental health of individuals. Agarwood incense inhalation has been used as a traditional Chinese medicine for relaxation and to improve sleep for centuries. In a previous study by the authors it was demonstrated that agarwood essential oil (AEO) injection exerted anxiolytic and antidepressant effects. Therefore the present study further investigated the anxiolytic and antidepressant effects of AEO inhalation on anxiolytic mice induced by M-chlorophenylpiperazine and depressive mice induced by chronic unpredictable mild stress. The results demonstrated that AEO exerted a significant anxiolytic effect, whereby autonomous movements were inhibited during the light dark exploration test and open field test. Furthermore, the tail suspension test and the forced swimming test demonstrated that AEO also exerted an antidepressant effect, whereby the immobility times were decreased. Moreover, AEO was determined to increase the levels of 5-hydroxytryptamine, γ-aminobutyric acid (GABA) A receptor (GABAA) and glutamate (Glu) in anxiolytic mice and inhibit the levels of GABAA and Glu in depressive mice. Further investigations into how AEO affected the Glu/GABA system demonstrated that AEO markedly increased the protein expression levels of GABA transaminase (GABAT), glutamate metabotropic receptor 5 (GRM5), glutamate ionotropic receptor AMPA type subunit 1 (GluR1) and vesicular glutamate transporter 1 (VGluT1). Furthermore, AEO reduced the expression levels of GABAT, glutamate ionotropic receptor NMDA type subunit 2B and GRM5, and enhanced the expression levels of GluR1 and VGluT1. These results demonstrated that AEO potentially possesses antianxiety and antidepressant properties. The present study determined that the mechanism was related to the regulation of Glu/GABA neurotransmitter system homeostasis.

Pharmacological and In-Silico Investigations of Anxiolytic-like Effects of Phyllanthus Fraternus: A Probable Involvement of GABA-A Receptor

Background:: Phyllanthus fraternus Webster Linn (family, Euphorbiaceae) is used as a traditional medication for the treatment of various disorders and has therapeutic implications. Objective:: This study intends to investigate the anxiolytic potential of Phyllanthus fraternus standardized extract and prediction of the probable role of its marker phytoconstituents. Methods:: We tested the standardized hydro-ethanolic extract of Phyllanthus fraternus (whole plant) for the Elevated plus-maze model (EPM) and Light & Dark Exploration test as classical models for anxiety. Phyto-chemical HPTLC fingerprint analysis was performed for the detection of two classes of compounds lignans and tannins. HPTLC analysis of the standardized extract was performed using phyllanthin hypophyllanthin and corilagin as marker compounds. Additionally, GABA receptor antagonism was studied in other sets of experiments to assess the involvement of this receptor in the anxiolytic- like effects produced by Phyllanthus fraternus. Results:: The lower doses of the lignan and tannin-rich extract of the Phyllanthus fraternus possess significant anxiolytic-like activity compared to the standard diazepam. Additionally, the results of the present study suggested that high doses (400mg/kg) of Phyllanthus fraternus have exerted some sedative- like effects. Phytochemical screening and HPTLC fingerprint analysis indicate the presence of lignans and tannins, whereas HPLC analysis of the standardized extract revealed the presence of marker lignan (Hypophyllanthin) and Tannin (Corilagin). The anxiolytic-like effect of Phyllanthus fraternus observed in the mice models were blocked by Flumazenil indicating the involvement of GABAA receptors in the modulation of this effect. Our molecular docking studies also supported probable anxiolytic and sedative effects. Conclusion:: To summarize, results support the use of Phyllanthus fraternus in the anxiety-like symptoms/ disease condition and suggest its anxiolytic-like effect governed by the GABA-A receptors.

Identification of Anxiolytic Potential of Niranthin: In-vivo and Computational Investigations

Anxiety is an unpleasant state, which can critically decrease the quality of life is often accompanied by nervous behaviour and rumination. Niranthin is a lignan isolated from various Phyllanthus sources. The literature survey on niranthin highlights wide ranges of the therapeutic potentials. In a present study, based on our previous investigations, we evaluated pure, isolated and characterized niranthin as an anxiolytic agent. The niranthin [6-[(2R,3R)-3-[(3,4-dimethoxyphenyl)methyl]-4-methoxy-2-(methoxymethyl)butyl]-4-methoxy-1,3-benzodioxole] was purchased from commercial source and further subjected for assessment of its anxiolytic potentials using popular animal models including Elevated plus-maze model/test (EPM) and Light & Dark Exploration test (L&D). GABA-A receptor mediation was evaluated by pretreating the mice with the GABA-A receptor antagonist Flumazenil before the EPM task. Molecular docking simulation studies (pdb id: 4COF) carried out by Vlife QSAR software showed that niranthin (docking score: − 62.1714 kcal/mol) have shown comparatively best docking score compared to the standard drug Diazepam (docking score: − 63.1568 kcal/mol). To conclude, Niranthin has probable potential in the management of anxiety disorder. Our in-silico and in-vivo analysis (indirectly) indicated the plausible role of GABA mediation for anxiolytic activity. Although, these studies are preliminary, future in depth experimental explorations will be required to use Niranthin as anti-anxiety drug in near future.Graphic

An Insight Into the Anxiolytic Effects of Lignans (Phyllanthin and Hypophyllanthin) and Tannin (Corilagin) Rich Extracts of Phyllanthus amarus : An In-Silico and In-vivo approaches.

This investigation was aimed at exploring the anxiolytic potential of Phyllanthus amarus standardized extracts and predict probable role of marker phyto constitutents. Three standardized extracts of Phyllanthus amarus plant viz. standardized aqueous extract of Phyllanthus amarus whole plant (PAAE), standardized methanolic extract of P. amarus leaf (PAME) and the standardized hydro-methanolic extract of P. amarus leaf (PAHME) were tested in the classical animal models of anxiety: Elevated plus-maze model and Light & Dark Exploration test. The lower doses of the tannin rich extract (PAHME) of the P. amarus possess significant anxiolytic activity compared to lignin rich (PAME) and aqueous extracts (PAAE), while at a higher dose (400mg/kg) the results of all three extracts appears to be potentially sedative. While the molecular docking studies support these probable anxiolytic, the sedative effects of the Phyllanthus amarus extracts could be due to the interaction of tannins and lignans with the GABAbenzodiazepine receptor complex. The results of the present study indicate that the tannin-rich extract of the P. amarus may have potential clinical applications in the management of anxiety. It can be further studied for optimum dosage to be used as a future of anti-anxiety drug development or as a standardized Phytomedicine.

Comparative studies on novel combinations of pregabalin plus venlafaxine with standard diazepam and marketed combination of alprazolam plus sertraline for anxiety disorders

Summary Objective- In present study, eleven novel dose combinations of Pregabalin & Venlafaxine from minimum effective dose to higher anxiolytic dose were taken for assessment of anxiolytic activity in Swiss mice.Method — Classical animal models of anxiety vise: Elevated plus-maze model and Light & Dark Exploration test Apparatus. Diazepam was used as a standard anxiolytic. In addition the combinations were also compared with a fixed dose marketed combination of Alprazolam & Sertraline (Anxit Plus).Result — The results of the study reveal that combinations of Pregabalin & Venlafaxine (serotonin norepinephrine reuptake inhibitor) have better anxiolytic efficacy, which is comparable to Diazepam and Alprazolam-Sertraline combination.Conclusion- Further clinical studies are required for getting better idea about efficacy and clinical utility of Pregabalin-Venlafaxine combination.

Potential of Alternanthera philoxeroides on Improvement of Anxiety-Like Behavior Induced By Ovariectomized Mice Model

Abstract: Background: Ovariectomy (OVX) causes estrogen deprivation and oxidative stress leads to the hippocampus cell death and affected on mood disorders such as anxiety. Alternanthera philoxeroides was folk used for blood tonic and neuroprotective. Objectives: The action of A. philoxeroides extract (AP) on anti-anxiety in OVX mice model was evaluated and chromatographic fingerprint of AP was analyzed. Methods: Mice were ovariectomized to induce estrogen deprivation which involved anxiety. AP (250 and 500 mg/kg/day) and 17β-estradiol (E2, 1μg/kg/day) was treated. Six weeks after treatment, anxiety-like behavior was evaluated by the elevated plus maze test (EPM) and light/ dark exploration test (LD). Additionally, fingerprint of AP was characterised by high performance liquid chromatography (HPLC) technique. Results: E2 and AP 250 and AP 500 significantly diminished the anxiety behavior. Rutin, quercetin and kaempferol were detected in this plant. Conclusion: AP can manifest anti-anxiety in mice via estrogenic activity and it may action by rutin, quercetin and kaempferol. Key words: Alternanthera philoxeroides, Ovariectomy, Anxiety, Neuroprotective, Behavior, Flavonoids

Screening of Antistress and Anxiolytic Activities of Piper longum Fruits Extract

The aim of the study was to investigate adaptogenic and anxiolytic activities of methanol extract of Piper longum fruits at different dose levels (100, 250 and 500 mg/kg) using different experimental animal models. In the present research work antistress activity was assessed by swimming endurance and immobilization stress models, and anxiolytic activity were assessed by elevated plus maze behavior of mice, light dark exploration test in mice and open field apparatus test in rats. In swimming endurance test, the mean time of swimming performance and swimming stress induced biochemical parameters such as serum cortisol, the weights of adrenal glands, ascorbic acid and cortisol levels were recorded in the adrenal gland. There was dose dependent significant increase in swimming performance time observed in mice pretreated with graded doses of the test extracts. Animals pretreated with test extracts at different dose levels showed significant and dose dependent fall in all the biochemical parameters, as compared to the stress control animals. Treatment with standard and test extracts significantly reversed the stress induced altered hematological parameters, biochemical parameters, organs weight, GSH and LPO levels and neurotransmitters such as dopamine, nor adrenaline and serotonin levels in rat brain In immobilization stress. The test extracts demonstrated the significant increase in time spent and number of entries into open arm in elevated plus maze apparatus test and also increase in time spent and number of entries into lit box was observed in light box exploration test and reduction in time spent and number crossing into the dark compartment observed in animals pretreated with test extract. Pretreatment with test extracts demonstrated dose dependent significant increase in ambulation, rearing and self-grooming and significant decrease in fecal dropping in case of open field test.

Evaluation of antianxiety activity of ethanolic extract of leaves of Ocimum sanctum (tulsi) in albino mice

Background: Anxiety is a normal emotional behavior, however, becomes pathological precipitating cardiovascular and psychiatric disorders when it is severe. Many allopathic drugs are available to treat anxiety disorders, among which benzodiazepines are most commonly used which possess various systemic side effects. Aims and Objectives: In our study, we have attempted to evaluate new compound Ocimum sanctum (OS) in the hope of identifying the anxiolytics with fewer side effects as many plant products have been claimed to be free from side effects and less toxic than synthetic drugs. Materials and Methods: The anxiolytic activity of ethanolic extract of OS is evaluated with two validated modes, elevated plus maze and light and dark exploration test. A total of 60 animals (n = 60) were used. They were divided into five groups of six animals each for both models. The effects of the test drug OS at three different doses 1.75, 4.25, and 8.5 mg/kg were compared with the standard anxiolytic diazepam at 1 mg/kg dose and control group using 1% gum acacia at 10 ml/kg dose 1 h after administration of the drug. Results: The behavioral changes in both paradigms are suggestive of decreased anxiety, decreased aversion to light and increased exploratory behavior of the animal which is comparable changes produced by the standard drug diazepam concluding that OS has anxiolytic activity. Conclusion: OS has potential clinical application in the management of anxiety disorders. Further investigation of the mechanism/mechanisms of action of the plant extract, as well as the active substance/substances responsible for its biological actions, is necessary.

Exposure to short photoperiod regime reduces ventral subicular lesion-induced anxiety-like behavior in Wistar rats

Neurodegeneration of hippocampal structures is implicated in Alzheimer's disease (AD). Patients with AD exhibit ‘sundown syndrome’ featuring mood swings and anxiety. Although there are studies demonstrating circadian rhythm disruption associated with sundown phenomenon, the mechanisms underlying the emotional disturbances remain elusive. In the present study, we examined the relationship between subiculum (a key hippocampal output structure) and anxiety. Our study demonstrates that bilateral ventral subicular lesion (VSL) leads to anxiogenic behavior. In the elevated plus maze test, VSL rats made less number of entries into the open arms and spent significantly more time in the closed arms. Similarly, in the light–dark exploration test, VSL rats spent significantly more time in the dark chamber and made fewer entries into the light chamber. VSL also produced significant neurodegeneration in the paraventricular, suprachiasmatic and dorsomedial nuclei of the hypothalamus. Exposing VSL rats to a short photoperiod regime (SPR; 06/18h light–dark cycle) for 21days ameliorated the anxiety-like behavior. VSL rats on SPR also exhibited increased food consumption and higher core body temperature. Our study supports the hypothesis that the ventral subiculum regulates anxiety-like behavior and that SPR helps in the alleviation of such behavior. Even though the mechanisms underlying anxiolytic effects of light–dark cycle manipulation are yet to be elucidated, such non-pharmacological strategies can help to mitigate anxiety-like behavior. A proper understanding of the effectiveness of photoperiod manipulation will help in developing strategies in the management of emotional disturbances associated with affective and neurodegenerative disorders including AD.

Differential effects of subchronic Phencyclidine on anxiety in the light-enhanced startle-, light/dark exploration- and open field tests

Subchronic treatment with the N-methyl-d-aspartate receptor antagonist phencyclidine (PCP) is a valuable approach to model the symptomatology of schizophrenia, a multi-facetted psychiatric disorder, in rodents.We addressed the question whether subchronic PCP (scPCP) treatment (5mg/kg bidaily for 7 days) would affect anxiety in rats, since contradictory findings have been reported so far. Anxiety-like behaviour was assessed using the light-enhanced startle paradigm (LES), a method which measures the effect of the natural aversion to light on the startle reflex and does not depend on motivated behaviour or exploratory drive. For comparison, anxiety-like behaviour was measured in the light–dark exploration test (LDT) and in an open field environment (OFT).The scPCP-treatment did not affect baseline startle reactivity or light-enhanced startle, suggesting normal anxiety levels in treated animals. Further, normal anxiety-like behaviour was also found in the OFT. In the LDT, scPCP treated rats displayed shorter latencies to enter the lit compartment and shuttled more between the dark and lit compartments, behaviours indicative of decreased anxiety and/or increased exploratory activity.Our findings therefore suggest that the effects of scPCP-treatment on anxiety-like behaviour are task-dependent and recommend the additional use of tests independent from exploratory drive or other motivated behaviours, such as the LES paradigm.

The effects of phencyclidine (PCP) on anxiety-like behavior in the elevated plus maze and the light–dark exploration test are age dependent, sexually dimorphic, and task dependent

Previous research in our laboratory revealed sexually dimorphic effects of prior exposure to phencyclidine (PCP) on elevated plus maze behavior. In an attempt to examine the developmental time course of this effect and determine the extent to which it generalizes to other anxiety paradigms, young adult (61–64days old) and adult (96–107days old) male and female rats were treated with PCP (15mg/kg) or saline. Following a two week withdrawal period, animals were tested in either the elevated plus maze (EPM) or a light–dark exploration (LD) test. In adults, both tests revealed a sexually dimorphic effect driven by PCP-induced decreases in anxiety in females as indicated by increased time spent in the open arms of the EPM and in the lit compartment of the LD test and increased anxiety in males as indicated by decreased time spent in the lit compartment of the LD. In young animals, PCP pretreatment decreased open arm exploration in the elevated plus maze, indicating increased anxiety. However, PCP increased time spent in the light compartment in the light–dark exploration test, indicating decreased anxiety. Corticosterone levels measured 15min after the onset of the EPM failed to reveal an association between the behavioral effects of PCP and corticosterone levels. The results in adults substantiate the previously observed sexually dimorphic effect of PCP on elevated plus maze behavior in adults and indicate that the effect generalizes to another anxiety paradigm. The results in the younger animals suggest an age dependent effect of PCP on anxiety in general and indicate that behaviors in the elevated plus maze and the light–dark exploration test reflect dissociable psychobiological states.

Decreased immobility in swimming test by homologous interferon-α in mice accompanied with increased cerebral tryptophan level and serotonin turnover

Animal models are used to decipher the pathophysiology of IFN-α-induced psychiatric complications in humans. However, the behavioral effects of IFN-α in rodents remain highly controversial. In contrast to homologous IFN-α, our recent study revealed that human IFN-α, which was used in many previous investigations, had no biological activity in mice. To evaluate the behavioral effects of homologous IFN-α in mice, adult C57BL/6J mice were treated with carrier-free murine IFN-α and tested on a number of behavioral paradigms. Surprisingly, contrary to previous reports, IFN-α treatment decreased the time spent immobile in the forced-swimming test after a single intraperitoneal injection at 2×106IU/kg, whereas general locomotor activity was not altered. The elevated plus-maze (EPM) test showed a trend toward an increased anxiety profile in IFN-α-treated mice. The tail-suspension and light dark exploration test revealed no difference between IFN-α-treated and control animals. Interestingly, neurochemical analysis revealed significantly increased concentrations of tryptophan and 5-hydroxyindoleacetic acid (5-HIAA)/serotonin (5-HT) ratios following IFN-α treatment in selected brain regions. Thus, systemic murine IFN-α treatment increases swimming time in mice. Increased cerebral serotonin turnover as well as increased tryptophan concentrations, induced by IFN-α, implicates serotonergic neurotransmission in behavioral dysfunction caused by this innate immune mediator.

Anxiolytic activity of Vitex negundo Linn. in experimental models of anxiety in mice.

The purpose of this study was to characterize the putative anxiolytic-like activity of an ethanolic extract prepared from the roots of Vitex negundo (VN) using the elevated plus maze (EPM) and light–dark exploration test in mice. Male mice were either treated orally with the VN extract or the positive control diazepam, respectively, 1 hour before behavioral evaluation. Oral administration of 100 and 200 mg/kg of VN extract significantly (P > 0.01) increased the percentage time spent on and the number of entries into the open arms of the EPM. The effect was comparable to that of the benzodiazepine diazepam (2 mg/kg p.o.). In light–dark exploration test, diazepam-treated rats significantly increased the time spent in light arena and decreased the duration of immobility, while VN treated rats also showed a significant (P >0.01) increase in the time spent (100 and 200 mg/kg) in light arena. Diazepam and the VN extracts do not produced any overt motor dysfunction. These results indicate that VN is an effective anxiolytic agent. In conclusion, the action of extract upon the anxiety models tested are in accord with the traditional use of VN L. and could be useful in primary medical care. Key words: Vitex negundo, anxiolytic, elevated plus maze, light–dark exploration, locomotor activity

Genetic Inactivation of the NMDA Receptor NR2A Subunit has Anxiolytic- and Antidepressant-Like Effects in Mice

There is growing evidence implicating the glutamate system in the pathophysiology and treatment of mood and anxiety disorders. Glutamatergic neurotransmission is mediated by several receptor subfamilies including multiple NMDA receptor subunits (NR2A-D). However, little is currently understood about the specific roles of NMDA subunits in the mediation of emotional behavior due to a lack of subunit-specific ligands. In the present study, we employed a mouse gene-targeting approach to examine the role of the NR2A subunit in the mediation of anxiety- and depressive-related behaviors. Results showed that NR2A knockout (KO) mice exhibit decreased anxiety-like behavior relative to wild-type littermates (WT) across multiple tests (elevated plus maze, light-dark exploration test, novel open field). NR2A KO mice showed antidepressant-like profiles in the forced swim test and tail suspension test, as compared to WT controls. Locomotor activity in the nonaversive environments of the home cage or a familiar open field were normal in the NR2A KO mice, as were gross neurological and sensory functions, including prepulse inhibition of startle. Taken together, these data demonstrate a selective and robust reduction in anxiety- and depression-related behavior in NMDA receptor NR2A subunit KO mice. Present results support a role for the NR2A subunit in the modulation of emotional behaviors in rodents and provide insight into the role of glutamate in the pathophysiology and treatment of mood and anxiety disorders.

Orexin-A (hypocretin-1) is possibly involved in generation of anxiety-like behavior

Orexins (hypocretins) are neuropeptides expressed specifically in neurons in the lateral hypothalamic area and are known to be involved in the regulation of vigilance and feeding behavior. However, the relationship between orexin and emotional behaviors like anxiety is still poorly understood. Therefore, in this report we evaluated the effect of intracerebroventricular injection of orexin-A in two major anxiety tests, the light–dark exploration test (mouse) and the elevated plus-maze test (mouse, rat). Orexin increased time spent in the dark compartment in the light–dark test and time spent on the closed arms in the elevated plus-maze test. These results were not caused by a hypothetical sedative or activity-inducing effect of orexin-A because spontaneous locomotor activity did not alter upon orexin-A application under novel conditions. We therefore suggest an anxiogenic effect of orexin-A. To our knowledge, this is the first report about a relationship between orexin-A and anxiety.

Behavioural characterisation of transgenic mice overexpressing galanin under the PDGF-B promoter

The behavioural phenotype of transgenic mice (3-5-months old) overexpressing galanin (GalOE mice) under the platelet-derived growth factor B (PDGF-B) promoter was evaluated in a battery of tests, including locomotor cages, light-dark exploration test, elevated plus-maze and the Porsolt forced swim test. Learning and memory were assessed in the Morris water maze task. GalOE mice showed a slight increase in spontaneous locomotor activity assessed in the locomotor cages, but the amphetamine-induced increase in locomotor activity was somewhat lower in GalOE mice. Anxiety-like behaviour in light-dark exploration and elevated plus-maze tests did not differ between genotypes. In the Porsolt forced swim test, GalOE mice displayed an increased time of immobility, indicative of increased learned helplessness possibly reflecting increased stress-susceptibility and/or depression-like behaviour. GalOE mice showed normal learning and memory retention in the Morris water maze tasks. These data support the hypothesis that galanin may have a role in functions related to mood states, including affective disorders.

Anxiolytic-like actions of centrally-administered neuropeptide Y, but not galanin, in C57BL/6J mice

Neuropeptide Y (NPY) and galanin (GAL) are densely localized in brain regions subserving stress, fear and anxiety. While previous research supports a role for both neuropeptides in the mediation of rodent emotional behaviors, there is currently a lack of information on the effects of central administration of NPY and GAL on fear- and anxiety-related behaviors in mice. In the present study, the effects of intracerebroventricularly administered NPY and GAL were assessed in C57BL/6J mice on a battery of tests for fear- and anxiety-related behavior. NPY (0.5, 1.0 nmol) produced clear anxiolytic-like effects in the elevated plus-maze and light↔dark exploration test, whereas GAL (0.5, 1.0 nmol) was without effect. NPY (0.5 nmol) also increased locomotor activity in the open field test. In the fear conditioning paradigm, NPY administered prior to training reduced freezing to context (0.5, 1.0 nmol) and auditory cue (1.0 nmol). Pre-training GAL (0.5 nmol) treatment reduced freezing to context. Taken together, results demonstrate robust effects of centrally-administered NPY, but not GAL, on anxiety-like behaviors and fear conditioning in mice. These findings provide a basis for future studies of mice with targeted gene mutations, directed at delineating the anatomical regions and receptor subtypes mediating the effects of NPY and GAL on emotion.

The effect of neonatal handling on adult feeding behavior is not an anxiety-like behavior

Brief periods of handling during the neonatal period have been shown to have profound and long-lasting physiological consequences. Previous studies performed in our laboratory have demonstrated that handling the pups during the neonatal period leads to increased sweet food ingestion in adult life. The objective of this study is to verify if this effect could be explained by the enhanced anxiety levels in these animals. Litters were divided in: (1) intact; (2) handled (10min in an incubater/day) and (3) handled + tactile stimulation (10min/day). Procedures were performed on days 1–10 after birth. When adults, rats were tested in the elevated plus maze apparatus, light dark exploration test and open field test. They were also tested for sweet food ingestion, being injected with 2mg/kg diazepam or vehicle 60min before the test. Handling and handling + tactile stimulation do not alter performance in the plus maze test, but handled rats presented more crossings in the light/dark exploration test and open field (two-way ANOVA). Females also spent more % time in the open arms in the plus maze and more time in the lit compartment in the light/dark test, presenting more crossings in both tests. Both treated rats (handled and handled + tactile stimulation groups) consumed more sweet food than intact ones (two-way ANOVA). When diazepam was injected prior to the measurement of sweet food ingestion, there was no effect of the drug. We suggest that handling during the neonatal period leads to plastic alterations in the central nervous system of these animals, causing an increased ingestion of palatable food in adult life, and this alteration does not express an anxiety-like behavior.

Behavioural characterisation of young adult transgenic mice overexpressing galanin under the PDGF-B promoter

The behavioural phenotype of transgenic mice (3- to 5-months old) overexpressing galanin (GalOE) under the platelet-derived growth factor B (PDGF-B) promoter was evaluated in a battery of tests, including open field, locomotor cages, light–dark exploration test, elevated plus-maze and the Porsolt forced swim test. Learning and memory were assessed in the passive avoidance and the Morris water maze tasks. No difference between genotypes was found in exploratory activity in the open field. GalOE mice showed a slight increase in spontaneous locomotor activity assessed in the locomotor cages, but the amphetamine-induced increase in locomotor activity was somewhat lower in GalOE mice. Anxiety-like behaviour in the three different tests including open field, light–dark exploration and elevated plus-maze did not differ between genotypes. In the Porsolt forced swim test, GalOE mice displayed an increased time of immobility, indicative of increased learned helplessness possibly reflecting increased stress-susceptibility and/or depression-like behaviour. GalOE mice showed normal learning and memory retention in the passive avoidance and the Morris water maze tasks. These data support the hypothesis that galanin may have a role in functions related to mood states including affective disorders.