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At least 1,135 records · Page 63Linked to original sources
PubMed2004

The selective serotonin-2A receptor antagonist M100907 reverses behavioral deficits in dopamine transporter knockout mice.

A hyperdopaminergic state in humans has been hypothesized to contribute to the pathology of a number of psychiatric illnesses, including schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder. Mice that display elevated synaptic levels of dopamine due to a genetically engineered deletion of the dopamine transporter (DAT) model behavioral deficits that simulate the above conditions. As novel treatment strategies for these disorders have focused on the serotonin (5-HT) 2A receptor, we determined the capacity of the highly selective 5-HT(2A) receptor antagonist M100907 to reverse behavioral deficits in DAT knockout (KO) mice. Prior to drug treatment, DAT KO mice exhibited increased levels of locomotor activity and highly linearized movement in a novel environment, as well as reduced prepulse inhibition (PPI) of acoustic startle, compared to wild-type littermates. Treatment with M100907 (0.3-1.0 mg/kg, but not 0.1 mg/kg) reversed locomotor deficits in DAT KO mice. Similarly, treatment with 1.0 mg/kg M100907 reversed the PPI deficits in DAT KO mice. These data indicate that selective 5-HT(2A) receptor antagonists, such as M100907, may represent a class of drugs that can be used to treat conditions in which a chronic, elevated dopaminergic tone is present and contributes to abnormal behavior and sensorimotor gating deficits.

Acoustic Stimulation↗
PubMed2001

How close is too close? A comparison of proxemic reactions of Singaporean Chinese to male intruders of four ethnicities.

Cultural and ethnic influence on proxemic behavior and invasions of personal space were investigated. 173 Chinese Singaporean undergraduates rated minimum interpersonal distance for perceived male intruders from four ethnic groups in Singapore--Malay, Indian, Chinese, and Caucasian. Rated distance scores ranked from "most distant" Indian Chinese dyads decreasing (in order of minimum distance) through Malay-Chinese. Caucasian-Chinese, and Chinese-Chinese dyads, independent of sex.

Adult↗
PubMed1999

A combined electrophysiological and video data acquisition system using a single computer.

Numerous experimental paradigms in behavioral electrophysiology and neuroethology require simultaneous recording of neural signals and behavior. A computer fitted with an analog to digital converter and a frame grabber was configured to perform both tasks. The analog to digital converter collected electrophysiological data while the frame grabber recorded video images. Since spike and image information were present in one computer, arbitrary combinations of electrophysiological and behavioral parameters could be used as the basis of an operant conditioning paradigm. The system was used to record subicular cell firing in rats performing a place search task. The computer monitored the output of the analog to digital converter for supra-threshold events. When one was detected, a block of samples (pre- and post-trigger) was stored in memory. The same computer also scanned every video frame to find the rat, and recorded a image of its behavior. The location of the rat was then quickly calculated. If it satisfied the task conditions, a brain reward pathway (medial forebrain bundle) was stimulated. The recording of neural and image data was monitored in real-time by writing spike waveforms and location data directly to video card RAM.

Algorithms↗
PubMed1998

Expression of testosterone conditioned place preference is blocked by peripheral or intra-accumbens injection of alpha-flupenthixol.

Previous evidence indicates that peripheral and intranucleus accumbens injections of testosterone have rewarding effects in male rats as measured in a conditioned place preference (CPP) paradigm. The present study investigated the neurochemical bases of the rewarding properties of testosterone by examining the effect of peripheral and intranucleus accumbens injection of the dopamine receptor antagonist alpha-flupenthixol on expression of testosterone-induced CPP. On alternating days, adult male Long-Evans rats received peripheral injections of testosterone in a water-soluble hydroxypropyl-beta-cyclodextrin (HBC) inclusion complex (0.8 mg/kg) or saline-HBC immediately prior to being confined for 30 min to one of two compartments of a place preference apparatus. All rats received 8 days of pairings (four hormone pairings, four saline pairings). On day 9 the rats were given a 20-min test session during which they had access to all compartments of the apparatus. No hormone was injected prior to the test session; however, rats received a peripheral (20 min prior; 0.2, 0.3 mg/kg) or intra-accumbens (2 min prior, 5.0 micrograms) injection of alpha-flupenthixol or saline. On the test day, rats receiving saline injections spent significantly more time in the compartment previously paired with injections of testosterone than in the compartment previously paired with vehicle injections. In contrast, rats receiving peripheral or intra-accumbens alpha-flupenthixol injections did not spend significantly more time in the compartment previously paired with testosterone. The blockade of testosterone CPP was not due to an effect of alpha-flupenthixol on motor behavior. The findings provide further evidence of the rewarding affective properties of testosterone and indicate that peripheral administration and intra-accumbens administration of alpha-flupenthixol block expression of testosterone CPP. The rewarding affective properties of testosterone are mediated, at least in part, via an interaction with the mesolimbic dopamine system.

Animals↗
PubMed1994

Clozapine attenuates cocaine conditioned place preference.

Clozapine, an atypical neuroleptic, has dopamine and serotonin antagonist actions that suggest its potential as a cocaine abuse pharmacotherapy. Yet, self-administration and discriminative stimulus studies in animals have reported both an enhancement and a partial blockade of cocaine's behavioral effects with clozapine. The present study examines further the effects of clozapine on cocaine conditioned place preference. Clozapine (10 mg/kg, s.c.) treatment significantly attenuated the development of cocaine (10 mg/kg, i.p.) conditioned place preference. These results, coupled with research that shows clozapine has limited extrapyramidal side effects, suggest that it should be considered as a pharmacotherapy for cocaine abuse.

Analysis of Variance↗
PubMed2004

The effects on place cells of local scopolamine dialysis are mimicked by a mixture of two specific muscarinic antagonists.

Using a dialysis probe near CA1 hippocampal recording electrodes, we infused nonspecific (scopolamine) and specific (methoctramine, pirenzepine) antagonists of muscarinic cholinergic transmission to determine their effects on the positional firing properties of place cells. Both low (0.5 mM) and high (2.0 or 3.0 mM) scopolamine significantly decreased in-field firing rate, increased the ratio of out-of-field to in-field rate, and reduced the smoothness of rate maps, while tending to increase out-of-field rate. Thus, local nonspecific muscarinic blockade mimicked the effects seen with intracerebroventricular application, suggesting that blockade of receptors local to the recorded cells plays an essential role. Unexpectedly, dialysis of scopolamine reduced locomotor activity, again duplicating the effects of intracerebroventricular administration. Most effects of methoctramine (1.0 mM), which blocks presynaptic m2 and m4 receptors, were initially strong but then diminished over hours. Methoctramine produced a significant increase only in out/in ratio and out-of-field rate, whereas it tended to increase in-field rate and monotonically decrease smoothness. Pirenzepine (3.0 mM), which blocks postsynaptic m1 receptors, produced a significant increase only in out/in ratio, whereas it tended to increase out-of-field rate and decrease in-field rate; all these effects were monotonic with respect to time. A mixture of methoctramine plus pirenzepine recapitulated the place-cell effects of scopolamine, although neither the mixture nor its separate components affected behavior. We conclude that the effects of scopolamine on place cells likely result from a combination of blockade of postsynaptic m1 receptors, leading to reduced excitability, with blockade of presynaptic m2 and m4 receptors, leading to increased out-of-field firing.

Action Potentials↗
PubMed1992

Age-related changes in spontaneous behavior and learning in NMRI mice from middle to old age.

Spontaneous behavior, sensorimotor reflexes and learning of 3-, 11-, 17- and 22-month-old virgin female NMRI mice were compared. Sensorimotor abilities decreased significantly from the age of 17 months in proportion to the muscular and equilibrium demand of the test. Open-field activity, hole board exploration as well as activity in the Y maze and plus maze decreased from the age of 11 months. However, in the open-field and Y maze, it was not possible to distinguish between 11-, 17- and 22-month-old mice, whereas in the plus maze, activity was drastically decreased in 17- and 22-month-old mice. In the plus maze, indices of fear-motivated behavior suggest a greater sensitivity to the situation in the age groups of 17 and 22 months. Spontaneous alternation also decreased from the age of 11 months, but at the age of 22 months, a rotational behavior emerged. Spatial learning was markedly impaired from middle age, i.e., 11 months, as indicated by longer latencies and absence of spatial bias in place learning. In cued learning, the 11- and 17-month groups eventually reached the level of the 3-month-old mice, while the 22-month age group remained impaired. Changes in swimming ability or speed did not appear to account for the swimming maze deficits. In contrast, a sensory or perceptual deficit cannot be excluded for the oldest mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed2004

Attenuation of cocaine-induced conditioned place preference by Polygala tenuifolia root extract.

A recent investigation indicated that Polygala tenuifolia Willdenow extract (PTE) possesses a potential antipsychotic effect. In this study, we examined the effects of PTE on the cocaine-induced changes in locomotor activity, conditioned place preference (CPP), fos-related antigen-immunoreactivity (FRA-IR), and activator protein (AP)-1 DNA binding activity. Cocaine-induced behavioral effects (hyperlocomotion and CPP) occurred in parallel with increases in FRA-IR and AP-1 DNA binding activity in the nucleus accumbens. These responses induced by cocaine were consistently attenuated by concurrent treatment with PTE (25 mg or 50 mg/kg/day, i.p. x 7). The adenosine A2A receptor antagonist, 1,3,7-trimethyl-8-(3-chlorostyrl)xanthine (0.5 or 1.0 mg/kg, i.p.), reversed the PTE-mediated pharmacological action in a dose related manner; neither the adenosine A(1) receptor antagonist, 8-cyclopentyl-1,3-dimethylxanthine (0.5 or 1.0 mg/kg, i.p.) nor the A2B receptor antagonist, alloxazine (1.5 or 3.0 mg/kg, i.p.) significantly affected this pharmacological action. Our results suggest that PTE prevents cocaine-induced behavioral effects, at least in part, via the activation of the adenosine A2A receptor.

Analysis of Variance↗
PubMed2005

An anatomically constrained, stochastic model of eye movement control in reading.

This article presents SERIF, a new model of eye movement control in reading that integrates an established stochastic model of saccade latencies (LATER; R. H. S. Carpenter, 1981) with a fundamental anatomical constraint on reading: the vertically split fovea and the initial projection of information in either visual field to the contralateral hemisphere. The novel features of the model are its simulation of saccade latencies as a race between two stochastic rise-to-threshold LATER units and its probabilistic selection of the target for the next saccade. The model generates simulated eye movement behavior that exhibits important characteristics of actual eye movements made during reading; specifically, simulations produce realistic saccade target distributions and replicate a number of critical reading phenomena, including the effects of word frequency on fixation durations, the inverted optimal viewing position effect, the trade-off between first and second fixation durations of refixated words, and the dependence of parafoveal preview benefit on eccentricity.

Eye Movements↗
PubMed2003

Developing a virtual reality-based methodology for people with dementia: a feasibility study.

The aim of this study was to examine the feasibility of virtual reality (VR) technology for use by persons with dementia (PWD). Data were obtained directly from six PWD regarding their experiences with a virtual environment (VE) of a large outdoor park. A user-centered method was developed to assess: (a) presence; (b) user inputs; (c) display quality; (d) simulation fidelity; and (e) overall system usability. The extent to which PWD could perform four functional activities in the VE was also investigated (e.g., mailing a letter). In addition, physical and psychological well-being of PWD while interacting with the VE was assessed objectively by recording heart rate during the VR sessions and subjectively with discrete questionnaire items and real-time prompts. Symptom profiles associated with simulator sickness were assessed with an adapted version of the Simulator Sickness Questionnaire. The study found that PWD to some extent experienced presence; perceived that objects were realistic and moved naturally; generally felt in control of the interaction; and demonstrated little difficulty using a joystick for navigation. The study also demonstrated that VR is an appropriate medium for assessing functional behavior within the context of an ecologically valid VE. PWD did not experience any significant increase in symptoms associated with simulator sickness, or detriments to their psychological and physical well-being. These findings demonstrated that it is feasible to work in VEs with PWD.

Aged↗
PubMed2002

Inhibition of cyclin-dependent kinases improves CA1 neuronal survival and behavioral performance after global ischemia in the rat.

Increasing evidence suggests that cyclin-dependent kinases participate in neuronal death induced by multiple stresses in vitro. However, their role in cell death paradigms in vivo is not well characterized. Accordingly, the authors examined whether cyclin-dependent kinase inhibition resulted in functionally relevant and sustained neuroprotection in a model of global ischemia. Intracerebroventricular administration of the cyclin-dependent kinase inhibitor flavopiridol, immediately or at 4 hours postreperfusion after a global insult, reduced injury in the CA1 of the hippocampus when examined 7 days after reperfusion. No significant protection was observed when flavopiridol was administered 8 hours after reperfusion. The tumor-suppressor retinoblastoma protein, a substrate of cyclin-dependent kinase, was phosphorylated on a cyclin-dependent kinase consensus site after the global insult; this phosphorylation was inhibited by flavopiridol administration. Importantly, flavopiridol had no effect on core body temperature, suggesting that the mechanism of neuroprotection was through cyclin-dependent kinase inhibition but not through hypothermia. Furthermore, inhibition of cyclin-dependent kinases improved spatial learning behavior as assessed by the Morris water maze 7 to 9 days after reperfusion. However, the histologic protection observed at day 7 was absent 28 days after reperfusion. These results indicate that cyclin-dependent kinase inhibition provides an extended period of morphologic and functional neuroprotection that may allow time for other neuroprotective modalities to be introduced.

Animals↗
PubMed1990

Visual tracking of moving targets by freely flying honeybees.

The ability of freely-flying honeybees to track moving targets was examined by training them to collect a reward on a target, and then videotaping their approach to the target while it was in motion. Training experiments were carried out with several groups of bees, using various colors for the target and the background. Computer-aided frame-by-frame analysis of video recordings was used to plot the instantaneous positions of the target, as well as the position and orientation of the approaching bee in three dimensions. The results show that bees are perfectly capable of tracking moving targets and landing on them. When the distance of the target is greater than 15 cm, approaching bees correct for angular deviations of the target from the midline, both in the horizontal and in the vertical plane. In either plane, the input variables that are important to the tracking system seem to be (1) the angular bearing of the target with respect to the midline, and (2) the angular velocity of the target with respect to the eye. The tracking control system tends to orient the bee such that the target is located frontally, at an angle of ca. 35 deg below the bee's long axis. The chromatic properties of tracking behavior were investigated by employing combinations of colors for the target and background such that the boundary between the target and the background presented a contrast that was visible either only to the green-sensitive receptors of the bee's eye, or only to the blue-sensitive receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Biochemical and behavioral effects of intrahippocampal AF64A in rats.

AF64A (ethylcholine aziridinium, 1 nmole) injected into the dorsal hippocampus of the rat decreased choline acetyltransferase activity there by 20% without greatly affecting adjacent areas. The decrease was maximal by 3 days, and persisted for at least 3 weeks. The acetylcholine concentration at the injection site was decreased by 25-30% from 3 days to 4 weeks. Rats were trained on a continuous reinforcement (CRF) food-reinforced lever press schedule and then injected bilaterally in the dorsal and ventral hippocampus. Subsequent switching to a daily CRF-extinction schedule resulted in increased responding during extinction compared to controls which persisted for at least 13 session. However, injection after switching schedules increased it for only 2 sessions. This indicates that the persistently increased extinction responding is due mainly to impaired learned habituation to a new schedule. Most of the extinction effect of the intrahippocampal AF64A was due to its injection at the dorsal site. Separate rats which were trained on the 8-arm radial maze task (a test of short-term spatial working memory) and injected as above only showed marginally impaired task performance even at higher doses. We conclude that even relatively minor, localized, cholinergic deficits confined to the hippocampus can produce significant learning and memory impairments in situations where intermediate or long term memory formation is required.

Acetylcholine↗
PubMed2001

Cognitive performances and locomotor activity following dentate granule cell damage in rats: role of lesion extent and type of memory tested.

Intradentate injection of colchicine is one of the techniques used to destroy granule cells. This study compared the behavioral effects of various amounts of colchicine (1.0, 3.0, and 6.0 microg; Col 1, Col 3, and Col 6, respectively) injected into the dentate gyrus of adult Long-Evans male rats. Starting 10 days after lesion surgery, behavioral testing assessed home-cage and open-field locomotion, alternation in a T-maze, water-maze, and radial-maze learning according to protocols placing emphasis on reference, and working memory. All of these tasks are sensitive to hippocampal disruption. Histological verifications showed that the extent of the lesions depends on the dose of colchicine (index of dentate gyrus shrinkage: -33% in Col 1, -54% in Col 3, and -67% in Col 6 rats). Colchicine dose-dependently increased nocturnal home cage activity (an effect found 10 days but not 5 months after surgery), but had no significant effect on open-field locomotion or T-maze alternation. A dose-dependent reference memory impairment was found during the acquisition of spatial navigation in the water maze; Col 3 and Col 6 rats were more impaired than Col 1 rats. During the probe trial (platform removed), control rats spent a longer distance swimming over the platform area than all rats with colchicine lesions. In the working memory version of the test, all rats with colchicine lesions showed significant deficits. The deficits were larger in Col 3 and Col 6 rats compared to Col 1 rats. The lesions had no effect on swimming speed. In the radial-maze test, there was also a dose-dependent working memory impairment. However, reference memory was disrupted in a manner that did not differ among the three groups of lesioned rats. Our data are in line with the view that the dentate gyrus plays an important role in the acquisition of new information and is an integral neural substrate for spatial reference and spatial working memory. They also suggest that damage to granule cells might have more pronounced effects on reference than on working memory in the radial maze. Finally, they demonstrate that part of the variability in the conclusions from previous experiments concerning the role of granule cells in cognitive processes, particularly in spatial learning and memory, may be due to the type of tests used and/or the extent of the damage produced.

Animals↗
PubMed1993

Correlation of severity of psychiatric patients' delusions with right hemispatial inattention (left-turning behavior).

Studies associate psychotic disorders with various forms of subtle inattention to the right hemispace (left-turning behavior). The authors examined the correlation between this dopamine-related sign and severity of delusions (presumably dopaminergic symptoms) in 20 psychotic patients. Delusions were significantly correlated with severity of left-turning bias, and this neurological sign accounted for 33% of the variance in severity of delusions.

Adolescent↗
PubMed1989

Agitation and touch in the nursing home.

The relationship between manifestations of agitated behaviors and interpersonal distance was examined in 24 nursing home residents with high agitation and severe cognitive impairment. Analysis indicated that agitated residents displayed divergent responses to touch: touch was related to an increase in aggressive behaviors and to a decrease in physically nonaggressive behaviors (e.g., strange movements). The positive relationship between aggressiveness and touching suggests that residents may interpret touching as a violation of their personal space. The finding that residents exhibited fewer strange movements when touched suggests that touching can act as a quieting and comforting form of communication. The implications of these findings for caregivers are discussed.

Aged↗
PubMed1990

Head-direction cells recorded from the postsubiculum in freely moving rats. I. Description and quantitative analysis.

This paper is a study of the behavioral and spatial firing correlates of neurons in the rat postsubiculum. Recordings were made from postsubicular neurons as rats moved freely throughout a cylindrical chamber, where the major cue for orientation was a white card taped to the inside wall. An automatic video/computer system monitored cell discharge while simultaneously tracking the position of 2 colored light emitting diodes (LEDs) secured to the animal's head. The animal's location was calculated from the position of one of the LEDs and head direction in the horizontal plane calculated from the relative positions of the 2 LEDs. Approximately 26% of the cells were classified as head-direction cells because they discharged as a function of the animal's head direction in the horizontal plane, independent of the animal's behavior, location, or trunk position. For each head-direction cell, vectors drawn in the direction of maximal firing were parallel throughout the recording chamber and did not converge toward a single point. Plots of firing rate versus head direction showed that each firing-rate/head-direction function was adequately described by a triangular function. Each cell's maximum firing rate occurred at only one (the preferred) head direction; firing rates at head directions on either side of the preferred direction decreased linearly with angular deviation from the preferred direction. Results from 24 head-direction cells in 7 animals showed an equal distribution of preferred firing directions over a 360 degrees angle. The peak firing rate of head-direction cells varied from 5 to 115 spikes/sec (mean: 35). The range of head-direction angles over which discharge was elevated (directional firing range) was usually about 90 degrees, with little, if any, discharge at head directions outside this range. Quantitative analysis showed the location of the animal within the cylinder had minimal effect on directional cell firing. For each head-direction cell, the preferred direction, peak firing rate, and directional firing range remained stable for days. These results identify a new cell type that signals the animal's head direction in its environment.

Animals↗
PubMed2004

Different pathways mediated by CCK1 and CCK2 receptors: effect of intraperitonal mrna antisense oligodeoxynucleotides to cholecystokinin on anxiety-like and learning behaviors in rats.

Cholecystokinin (CCK) and its analogs generate anxiety in humans and measurable anxiety-like behaviors in rats. CCK receptor blockers have been reported to have variable effects in the treatment of anxiety disorders. In a prior study, intracerebroventricular administration of CCK-antisense oligodeoxynucleotides (ASODN) for 3 days significantly diminished anxiety-like behavior in rats. Counter to our expectations, intraperitoneal (i.p.) administration of CCK-ASODN significantly increased anxiety-like behavior and impaired retention performance in the Morris water maze. The aim of the present study was to manipulate CCK-mediated anxiety-like behavior and spatial memory in rats by peripheral (i.p.) administration of ASODN to preproCCK in the presence of antagonists to CCK1 and CCK2 receptor subtypes to further elucidate the roles of these two receptors and better understand the effects of i.p. CCK-ASODN. CCK-ASODN was injected i.p. to rats five times at 24-hr intervals with and without administration of CCK1R antagonist PD135158 or CCK2 antagonist benzotrip. Control groups received injections of either a scrambled oligodeoxynucleotide (ScrODN) or vehicle. On Day 6, the rats were assessed in the elevated plus maze paradigm and in the Morris water maze. The rats were sacrificed and their blood was assessed for corticosterone, ACTH, and prolactin levels. The results show that i.p. CCK-ASODN significantly increased anxiety-like behavior and impaired retention performance in the Morris water maze, compared to both control groups, accompanied by increased plasma corticosterone and plasma ACTH concentrations. In contrast, administration of CCK-ASODN together with CCK2R antagonist, but not with CCK1R antagonist, significantly decreased anxiety-like behavior in rats, but still impaired retention performance in the Morris water maze paradigm. Lower levels of plasma corticosterone and ACTH in CCK-ASODN+CCK2R antagonist-treated rats accompanied the reduced anxiety-like behavior. The present study showed an anxiolytic effect of i.p. CCK-ASODN in the presence of CCK2R, but not CCK1R.

Adrenocorticotropic Hormone↗