A 3D SPATIAL NAVIGATION TASK FOR ASSESSING MEMORY IN RODENTS

In the present report we describe a 3-D maze spatial navigation task for rats based on a modification of an eight-arm radial maze. The arms radiating from a central platform can be presented in a horizontal plane either raised 10 cm above the level of a central platform or lowered 10 cm below. Memory of visited and non-visited arms can be guided by distinct internal cues (patterns) that are presented on panels set at the end of each arm. Rats are trained in three different maze configurations (eight session each) with arms set lowered, flattened or raised relative to a central platform. A food pellet is placed at the end of each arm and rats are allowed to make eight arm choices only, in each testing session. In this task rats perform better when moving uphill to raised arms than when moving on flattened arms or when moving downhill to lowered arms. It is likely that spatial navigation on raised arms is based on visual cues that were highly visible from the central platform. This result can be accounted for by the position of the rats' eyes that are placed laterally on the sides of their heads

Pre-training in a radial arm maze abolished anxiety and impaired habituation in C57BL6/J mice treated with dizocilpine

Familiarity can imply a reduction of fear and anxiety, which may render learning and memory performance insensitive to NMDA receptor antagonism. Our previous study indicates that MK-801 (dizocilpine), NMDA antagonist, increased anxiety and prevented the acquisition of a spatial memory task. Here, we examined whether MK-801 will produce anxiety in mice that were familiar with the test environment. Male C57BL/6J mice were exposed, one session a day for 7 days, to a 3D maze, which consisted of nine arms attached to upward inclined bridges radiating from a nonagonal platform. In this maze, high anxiety mice avoid the arms in the first sessions. One group of mice received saline (SAL) while a second group received MK-801 (MKD1), both on day one. A third group received saline in the first 3 sessions, and MK 801 in subsequent sessions (MKD4). Saline and MK-801 (0.1 mg/kg) were administered intraperitoneally 30 min before the test. MKD4 mice demonstrated an increase in bridge and arm visits, and reached arm/bridge entries ratio close to 1 in session 5. SAL mice also crossed frequently onto the arms, and reached a comparable ratio, but this was achieved with a lower number of arm visits. MKD1 mice demonstrated a reduced number of arm visits in each session compared to SAL and MKD4 mice. Dizocilpine produced anxiety in mice treated from day 1 of the test, but not in those treated from day 4. It also impaired habituation in animals familiar with the test environment; it produced sustained non-habituating hyperactivity

Effects of methimepip and JNJ-5207852 in Wistar rats exposed to an open-field with and without object and in Balb/c mice exposed to a radial-arm maze

The role of the histamine H3 receptor (H3R) in anxiety is controversial, due to limitations in drug selectivity and limited validity of behavioral tests used in previous studies. In the present report, we describe two experiments. In the first one, Wistar rats were treated with an H3R agonist (methimepip), and exposed to an open-field. In the second one, Balb/c mice were treated with H3R agonist (methimepip) or antagonist (JNJ-5207852), and exposed to an open space 3D maze which is a modified version of the radial-arm maze. C57BL/6J saline treated mice were included for comparisons. When exposed to an empty open field, Wistar rats spent more time in the outer area and made very low number of brief crossings in the central area. However, when an object occupied the central area, rats crossed frequently into and spent a long time in the central area. Administration of a range of different doses of methimepip (selective H3R agonist) reduced the entries into the central area with a novel object, indicating enhanced avoidance response. In the 3D maze, both Balb/c and C57BL/6J saline-treated mice crossed frequently onto the bridges that radiate from the central platform but only C57BL/6J mice crossed onto the arms which extend the bridges. This suggests that Balb/c mice are more anxious than C57BL/6J mice. Neither methimepip nor JNJ-5207852 (selective H3R antagonist/inverse agonist) induced entry into the arms of the maze, indicative of lack of anxiolytic effects

Effect of transcranial near infrared light 1068 nm upon memory performance in ageing healthy individuals: a pilot study.

Background: We present a pilot study of near infrared (NIR) 1068 nm transcranial photobiomodulation therapy (PBM-T). Impact upon motor function, memory, and processing speed in healthy individuals, over 45 years of age, was evaluated. Methods: PBM-T was performed at home using a transcranial phototherapy device, a helmet comprised of 14 air cooled LED panel arrays, with a peak wavelength of 1068 nm, full width at half maximum bandwidth of 60 nm and total average optical output power of 3.8 Watts. The device was used for 6 minutes twice daily on age-matched middle-aged subjects with normal intellectual function. The FDA-approved computerised assessment tool ANAM was adopted to quantify a series of cognitive and motor activities in the participating groups. Results: A significant improvement in motor function, memory performance and processing speed was observed in healthy individuals with PBM-T compared to the placebo group. No adverse effects were reported. Conclusions: PBM-T may be a promising new approach to improve memory in healthy middle-aged individuals

Identification of a Novel GABAA Receptor Channel Ligand Derived from Melissa officinalis and Lavandula angustifolia Essential Oils

Aims: Melissa officinalis (Mo) and Lavandula angustifolia (La) essential oils and their major constituents ((E) - caryophyllene, caryophyllene oxide, geranyl acetate, linalool, nerol, Oct-1-en-3-ol, 3-Octanone, myrcene, allo-ocimene, p-cymene and α- terpineol) assessed by GC-MS) which are shared by these two essential oils were probed in an attempt to identify the GABAAR ligand(s). Study Design: [35S] t-butylbicyclophosphorothionate (TBPS) radioligand binding assay to GABAA receptors. In vitro neuronal viability assay. Place and Duration of Study: School of Biological and Biomedical Sciences, Durham University, United Kingdom (December 2012 and January 2013). Results: One of the major component (s) of (Mo), trans-ocimene, inhibited [35S] (TBPS) binding to native GABAA receptors in a concentration-dependent manner with an apparent IC50 of 40μM. Concentrations (0.001 mg/ml) of whole (Mo) were shown to display modest beneficial effects upon neuronal viability while at a higher concentration (0.1 mg/ml) of (Mo) and (La) oils induced a neurotoxicity effect. Conclusion: These data provide the first evidence that allo-ocimene is an neuroactive GABAA R inhibitory component found in both (Mo) and (La), and represents a novel GABAA receptor channel chemotype derived from a natural product. - See more at: http://www.sciencedomain.org/abstract.php?iid=474&id=13&aid=4142#.VCFGHBbQpv

Long-Term Cognitive Deficits After Subarachnoid Hemorrhage in Rats

Background Cognitive dysfunction can be a long-term complication following subarachnoid hemorrhage (SAH). Preclinical models have been variously characterized to emulate this disorder. This study was designed to directly compare long-term cognitive deficits in the context of similar levels of insult severity in the cisterna magna double-blood (DB) injection versus prechiasmatic blood (PB) injection SAH models. Methods Pilot work identified blood injectate volumes necessary to provide similar mortality rates (20–25 %). Rats were then randomly assigned to DB or PB insults. Saline injection and naïve rats were used as controls. Functional and cognitive outcome was assessed over 35 days. Results DB and PB caused similar transient rotarod deficits. PB rats exhibited decreased anxiety behavior on the elevated plus maze, while anxiety was increased in DB. DB and PB caused differential deficits in the novel object recognition and novel object location tasks. Morris water maze performance was similarly altered in both models (decreased escape latency and increased swimming speed). SAH caused histologic damage in the medial prefrontal cortex, perirhinal cortex, and hippocampal CA1, although severity of injury in the respective regions differed between DB and PB. Conclusion Both SAH models caused long-term cognitive deficits in the context of similar insult severity. Cognitive deficits differed between the two models, as did distribution of histologic injury. Each model offers unique properties and both models may be useful for study of SAH-induced cognitive deficits. Keywords Subarachnoid hemorrhage – Cognitive dysfunction – Prechiasmatic blood injection model – Cisterna magna double blood injection model – Ra

Localisation of NMU1R and NMU2R in human and rat central nervous system and effects of neuromedin-U following central administration in rats

Rationale: Neuromedin-U (NmU) is an agonist at NMU1R and NMU2R. The brain distribution of NmU and its receptors, in particular NMU2R, suggests widespread central roles for NmU. In agreement, centrally administered NmU affects feeding behaviour, energy expenditure and pituitary output. Further central nervous system (CNS) roles for NmU warrant investigation. Objectives: To investigate the CNS role of NmU by mapping NMU1R and NMU2R mRNA and measuring the behavioural, endocrine, neurochemical and c-fos response to intracerebroventricular (i.c.v.) NmU. Methods: Binding affinity and functional potency of rat NmU was determined at human NMU1R and NMU2R. Expression of NMU1R and NMU2R mRNA in rat and human tissue was determined using semi-quantitative reverse-transcription polymerase chain reaction. In in-vivo studies, NmU was administered i.c.v. to male Sprague-Dawley rats, and changes in grooming, motor activity and pre-pulse inhibition (PPI) were assessed. In further studies, plasma endocrine hormones, [DOPAC + HVA]/[dopamine] and [5-HIAA]/[5-HT] ratios and levels of Fos-like immunoreactivity (FLI) were measured 20 min post-NmU (i.c.v.). Results: NmU bound to NMU1R (KI, 0.11±0.02 nM) and NMU2R (KI, 0.21±0.05 nM) with equal affinity and was equally active at NMU1R (EC50, 1.25±0.05 nM) and NMU2R (EC50, 1.10±0.20 nM) in a functional assay. NMU2R mRNA expression was found at the highest levels in the CNS regions of both rat and human tissues. NMU1R mRNA expression was restricted to the periphery of both species with the exception of the rat amygdala. NmU caused a marked increase in grooming and motor activity but did not affect PPI. Further, NmU decreased plasma prolactin but did not affect levels of corticosterone, luteinising hormone or thyroid stimulating hormone. NmU elevated levels of 5-HT in the frontal cortex and hypothalamus, with decreased levels of its metabolites in the hippocampus and hypothalamus, but did not affect dopamine function. NmU markedly increased FLI in the nucleus accumbens, frontal cortex and central amygdala. Conclusions: These data provide further evidence for widespread roles for NmU and its receptors in the brain

Open space anxiety in rodents: the elevated platform with steep slopes

This report describes a behavioral test protocol for assessing anxiety in mice and rats in single or multiple sessions. The test is based on exposure of animals to an open-space elevated platform with suspended steep slopes attached on two opposite sides. In this test, all animals cross frequently onto and spend more time in the areas adjacent to slopes than in the areas adjacent to a void space. Balb/c mice (albinos) were shown consistently to be more anxious than CD-1 mice (albinos), c57/Bl6J and c57/Bl6N (pigmented) mice; they do not cross onto the slopes. When Balb/c mice are treated with amphetamine or diazepam, the number of crossings on the platform is signifi cantly increased but only diazepam-treated mice do cross onto the slopes. In the presence of a protected space on the platform, the behavior of c57/Bl6J compares to that of Balb/c mice; they stop crossings onto the slopes and demonstrate avoidance response. Unlike the current existing tests, the present open-space anxiety test demonstrates reliable and consistent results with strong construct and discriminant validity. It provides unequivocal measures of fear-induced anxiety, which are not confounded with measures of fear-induced escape/avoidance responses, hyperactivity or impulsive responses

Effects of amphetamine and medial septal lesions on acquisition and retention of radial maze learning in rats

Procholinergic drugs have failed to overcome the memory deficit induced by alterations of the cholinergic system because their neurochemical target in the brain is either lacking or disorganised. However, there are many reports on a relative involvement of the dopaminergic system in learning and memory that may compensate for the cholinergic deficit because of the interaction or balance between neurotransmitters and the redundancy of the brain. The aim of our experiments is to examine the activation of the dopaminergic system on the performance of normal and medial septal lesioned rats in the radial maze test involving continuous choices. In the first experiment different groups of normal rats were treated with either 0.5, 1.0 or 2.0 mg/kg of D-amphetamine and tested in the radial maze. In the second experiment, medial septal lesioned rats which had learnt pre-op the radial maze test were retested a month later. Amphetamine had no effect on the memory measures provided by the radial maze test in normal and lesioned rats, but non-memory measures were significantly affected: amphetamine decreased the sequential choice responses and the time taken by the rats to perform the test. The present results show that the activation of the dopaminergic system does not compensate for the alteration of the cholinergic activity inducing amnesia, however, they support the recent data on the improving effect of amphetamine on locomotor activity. The interpretation of drug/lesion interaction effects is discussed in this paper in relation to the literature on the effect of promnesic drugs

One-trial object recognition in rats and mice: methodological and theoretical issues.

The one-trial object recognition task involves memory of a familiar object in parallel with the detection and encoding of a novel object. It provides the basis for the study of a wide range of cognitive and neuropsychological functions and processes in rats and mice. However, unlike in humans, primate and pigeon studies, object recognition in rats and mice has been mostly limited to memory while little is known about object perception, affordances and acquisition of a representation of an object. In the present paper, we addressed some of these issues. We also described novelty preference models and hypotheses that account for one-trial object recognition and question the validity of the novelty preference concept. In addition, we discussed whether one-trial object recognition involves working memory and how it involves memory of an episode