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At least 1,009 records · Page 56Linked to original sources
PubMed2002

Sensorimotor functions in transgenic mice expressing the neurofilament/heavy-LacZ fusion protein on two genetic backgrounds.

NFH-LacZ transgenic mice are characterized by expression of a non-endogenous fusion protein between a truncated form of mouse NFH (neurofilament of heavy molecular weight) and the complete Escherichia coli beta-galactosidase protein. These transgenic mice were compared to their respective controls on two background strains (C3H and FVB) in several sensorimotor tests. NFH-LacZ mice were deficient in tests requiring balance and equilibrium in a manner generally independent of genetic background. In particular, NFH-LacZ mice fell more quickly than controls from two stationary beams and had fewer rears in an open-field. The transgenic mice were also impaired during the initial trials of sensorimotor learning on the rotorod. We conclude that despite the absence of overt signs of sensorimotor weakness in their home cage, the disruption of the NFH gene, causing neurofilament accumulations in the cell body and diminished axonal calibers of motoneurons, is sufficient to cause motor deficits that resemble the early stages of amyotrophic lateral sclerosis.

Animals↗
PubMed2005

Identification of glyoxalase-I as a protein marker in a mouse model of extremes in trait anxiety.

For >15 generations, CD1 mice have been selectively and bidirectionally bred for either high-anxiety-related behavior (HAB-M) or low-anxiety-related behavior (LAB-M) on the elevated plus-maze. Independent of gender, HAB-M were more anxious than LAB-M animals in a variety of additional tests, including those reflecting risk assessment behaviors and ultrasound vocalization, with unselected CD1 "normal" control (NAB-M) and cross-mated (CM-M) mice displaying intermediate behavioral scores in most cases. Furthermore, in both the forced-swim and tail-suspension tests, LAB-M animals showed lower scores of immobility than did HAB-M and NAB-M animals, indicative of a reduced depression-like behavior. Using proteomic and microarray analyses, glyoxalase-I was identified as a protein marker, which is consistently expressed to a higher extent in LAB-M than in HAB-M mice in several brain areas. The same phenotype-dependent difference was found in red blood cells with NAB-M and CM-M animals showing intermediate expression profiles of glyoxalase-I. Additional studies will examine whether glyoxalase-I has an impact beyond that of a biomarker to predict the genetic predisposition to anxiety- and depression-like behavior.

Analysis of Variance↗
PubMed2001

The alpha(2a)-adrenergic receptor plays a protective role in mouse behavioral models of depression and anxiety.

The noradrenergic system is involved in the regulation of many physiological and psychological processes, including the modulation of mood. The alpha(2)-adrenergic receptors (alpha(2)-ARs) modulate norepinephrine release, as well as the release of serotonin and other neurotransmitters, and are therefore potential targets for antidepressant and anxiolytic drug development. The current studies were undertaken to examine the role of the alpha(2A) subtype of alpha(2)-AR in mouse behavioral models of depression and anxiety. We have observed that the genetic knock-out of the alpha(2A)-AR makes mice less active in a modified version of Porsolt's forced swim test and insensitive to the antidepressant effects of the tricyclic drug imipramine in this paradigm. Furthermore, alpha(2A)-AR knock-out mice appear more anxious than wild-type C57 Bl/6 mice in the rearing and light-dark models of anxiety after injection stress. These findings suggest that the alpha(2A)-AR may play a protective role in some forms of depression and anxiety and that the antidepressant effects of imipramine may be mediated by the alpha(2A)-AR.

Adrenergic Uptake Inhibitors↗
PubMed2003

Norepinephrine in the prefrontal cortex is critical for amphetamine-induced reward and mesoaccumbens dopamine release.

Increasing evidence points to a major involvement of cortical areas in addictive mechanisms. Noradrenergic transmission in the medial prefrontal cortex (mpFC) has been shown to affect the motor effects of amphetamine, although there is no evidence of its involvement in the rewarding effects of this psychostimulant. The present experiments were aimed at investigating the possibility of a selective involvement of prefrontal cortical norepinephrine (NE) in the rewarding-reinforcing effects of amphetamine. To do so, we evaluated the effects of mpFC NE selective depletion in mice of C57BL/6J inbred strain, a background commonly used in molecular approaches that is known to be highly susceptible to the rewarding effects of the psychostimulant. In a first set of experiments, we demonstrated the absence of amphetamine-induced conditioned place preference in mice bearing prefrontal NE depletion. In a second series of experiments, we demonstrated that the same lesion dramatically reduced amphetamine-induced mesoaccumbens dopamine release as measured by intracerebral microdialysis. These results indicate that noradrenergic prefrontal transmission, by allowing increased dopamine release in the nucleus accumbens induced by amphetamine, is a critical factor for the rewarding-reinforcing effects of this drug.

Amphetamine↗
PubMed1985

Adrenalectomy fails to alter radial maze performance of rats at retention intervals of 24 hours or less.

Evidence suggests that the behavioral actions of adrenalectomy and glucocorticoid replacement therapy result from changes in the binding of corticosterone to specific receptors in the hippocampus. Efficient foraging for bait on the radial maze has been demonstrated to require a functionally intact hippocampal system. The present experiment examined the effect of adrenalectomy on the ability of rats to locate unexplored arms in the radial maze after various retention intervals midway through completion of the maze. Rats were very proficient at locating the unexplored arms after retention intervals of 3 hours or less; significantly more trials were required to locate all of the previously unvisited arms at retention intervals of 8 and 24 hours. However, adrenalectomy failed to alter maze performance at any retention interval tested. It was concluded that the neural substrates involved in the performance of this spatial/working memory task are not dependent upon the neuromodulatory effects of physiological levels of adrenal corticosteroids. The results are discussed in terms of behavior/contingency conflicts and innate versus learned responses as factors which may be important for revealing behavioral actions of adrenalectomy or corticosteroid therapy.

Adrenal Cortex Hormones↗
PubMed1994

Differential effects of amphetamine and haloperidol on recovery after global forebrain ischemia.

Gerbils subjected to sham surgery or to bilateral occlusion of the carotid arteries were given an injection, during the recovery period, of saline, d-amphetamine, or haloperidol. The animals were subsequently tested once daily for 50 days in an eight-arm radial maze. Global forebrain ischemia had no effect on learning to avoid unbaited arms (reference memory), but greatly increased the number of times animals reentered previously visited arms (working memory errors). Gerbils made ischemic and treated with amphetamine reduced working memory errors more rapidly than did saline-treated ischemic gerbils; conversely, animals made ischemic and treated with haloperidol made more working memory errors than the ischemic controls. Although all ischemic animals were hyperactive, the differential radial maze behaviors of the ischemic groups cannot be explained on the basis of increased activity.

Animals↗
PubMed1988

Constraints on water maze spatial learning in rats: implications for behavioral studies of brain damage and recovery of function.

In an effort to develop spatial learning tasks not requiring food or water deprivation for use in studies of recovery of function after brain damage, T-maze spatial alternation learning was examined in intact rats using water maze swim-escape procedures. Consistent with previous studies, rewarded spatial alternation involving food or water deprivation was readily learned by intact rats. However, none of the groups of rats trained in the swim-escape tasks learned to alternate goal arm choices in the water maze at reliable rates. This was true regardless of whether non-correction or correction procedures were used, and regardless of intertrial delay intervals. Although average alternation rates over sessions did increase from chance levels, the majority of the rats did not reach criterion levels, even with as many as 38 consecutive days of testing. In contrast, a conditional spatial alternation task in the water maze, using a win-shift procedure, was readily learned. Surprisingly, a win-stay version of this conditional spatial task was not learned over 21 days of testing. These unexpected constraints on spatial learning and memory processes in rats cannot be attributed simply to failure of spatial information processing, nor to strict limitations on working memory in swim-escape tasks, since excellent spatial navigation abilities have been documented, and mastery of at least some working-memory tasks have now been demonstrated in swim-escape tasks.

Animals↗
PubMed1986

Huddling and independent feeding of neonatal rats can be facilitated by a conditioned change in behavioral state.

Infant rat pups were exposed to a novel odor (orange or cedar) while they received tactile stimulation (stroking of the body) or were presented with odor or stroking alone. The effects of these treatments were assessed on pups' performance in a huddling test (Experiment 1 and 2) and an independent feeding test (Experiment 3). During these tests, only pups that had received the simultaneous presentation of the odor and stroking exhibited an increase in huddling and feeding. The increase in these behaviors was dependent on the presence of the conditioned odor during testing.

Animals↗
PubMed2005

Biochemical and behavioural phenotyping of a mouse model for GAMT deficiency.

Deficiency of guanidinoacetate N-methyltransferase (GAMT) is the first described creatine (CT) deficiency syndrome in man, biochemically characterized by accumulation of guanidinoacetic acid (GAA) and depletion of CT. Patients exhibit severe developmental and muscular problems. We created a mouse model for GAMT deficiency, which exerts biochemical changes comparable with those found in human GAMT-deficient subjects. CT and creatinine (CTN) levels are significantly decreased and GAA is increased in knockout (KO) mice. In patients, other guanidino compounds (GCs) appear to be altered as well, which may also contribute to the symptomatology. Extensive evaluation of GCs levels in the GAMT mouse model was therefore considered appropriate. Concentrations of 13 GCs in plasma, 24-h urine, brain and muscle of GAMT mice were measured. We also report on the detailed behavioural characterization of this model for GAMT deficiency. Besides an increase of GAA and a decrease of CT and CTN in plasma, 24-h urine, brain and muscle of KO mice, we observed a significant increase of other GCs in brain and muscle that was sometimes reflected in plasma and/or urine. KO mice displayed mild cognitive impairment. In general, it could be concluded that the GAMT mouse model is very useful for biochemical research of GAMT deficiency, but shows only a mild cognitive deficit.

Animals↗
PubMedDate not supplied

Effects of dizocilpine (MK-801) on circling behavior, swimming activity, and place preference in zebrafish (Danio rerio).

Glutamate transmission plays an important role in many behavioral systems, including motor activity, learning, and memory. The noncompetitive NMDA receptor antagonist (+)MK-801 has been shown to increase motor activity and impair learning and memory in a variety of tasks in rats, mice, and other species. In an attempt to characterize the effects of MK-801 on motor activity and cognitive performance in an emerging neurobehavioral model, the zebrafish (Danio rerio), we examined the effects of MK-801 on circling behavior, swimming activity, and latency to enter, as well as preference for, an enriched chamber (EC). In Experiment 1, the effects of a 37-min acute exposure to (+)MK-801 (0, 2.0, and 20.0 microM) on circling behavior were measured in a round observation chamber. (+)MK-801 was observed to increase circling behavior in a dose-dependent manner. In the second experiment, fish were treated with 0, 2, 20, or 200 microM (+)MK-801 for 1 h, and swimming activity was measured in a rectangular observation chamber for 60 min following dosing. The lowest dose of (+)MK-801 decreased swimming activity. In the third experiment, fish were treated with either 0 or 20 microM (+)MK-801 for 1 h each day over four consecutive days. The fish were tested in a modified T-maze to assess both latency to enter, and preference for, an EC 24, 27, and 48 h after the last treatment. The results showed that untreated fish exhibited a preference for the EC at the 27- and 48-h trials, but (+)MK-801-treated fish did not exhibit a preference for the EC at any trial. No significant reduction in latency to enter the chamber was found for either treated or control fish. Together, the results of these experiments suggest that NMDA receptor antagonism (1) increases circling behavior, (2) alters swimming activity, and (3) impairs place preference. These findings lend further support for the usefulness of the zebrafish for assessing the acute and chronic exposure effects of water-soluble compounds on motor and cognitive functions.

Animals↗
PubMed2001

A comparison of chronic aspartame exposure to aspirin on inflammation, hyperalgesia and open field activity following carrageenan-induced monoarthritis.

The purpose of the present study was to investigate whether chronic aspartame exposure possesses analgesic and anti-inflammatory actions in the carrageenan-induced monoarthritis model similar to those properties of aspirin. Prior research demonstrated that aspartame can reduce second phase formalin pain and increase motor activity in arthritic patients. Fifty-eight male Sprague-Dawly rats were treated with aspartame (25, 50, 100 mg/kg) or saline for six days. An additional group of animals received daily injections of saline and on the sixth treatment day, received a 150-mg/kg dose of aspirin 30-minutes prior to behavioral testing. On Day 6, animals received an intra-articular (i.a.) injection of 2% lambda carrageenan (CARR) or an equal volume of saline and were tested four hours later on threshold to mechanical and thermal stimuli, open field activity, and knee joint diameter. Aspirin-treated arthritic animals exhibited significantly less mechanical hyperalgesia and knee joint inflammation compared with vehicle treated arthritic animals. However, aspirin did not reverse thermal hyperalgesia or increase motor activity to control levels. Aspartame did not reduce inflammation, increase motor activity, or attenuate thermal allodynia, but at 50 mg/kg did attenuate mechanical allodynia compared with vehicle treated arthritic animals. The anti-hyperalgesic effect on mechanical hyperalgesia was not seen at 25 mg/kg or 100 mg/kg aspartame. These results suggest that a certain amount of aspartame may provide relief of arthritic pain to a similar degree as aspirin in some individuals. The specific effect of aspartame and aspirin on mechanical hyperalgesia should be considered when these agents are used for the therapeutic treatment of arthritic conditions.

Animals↗
PubMed2005

Behavioral effects of basal forebrain cholinergic lesions in young adult and aging rats.

The interactive effects of age and cholinergic damage were assessed behaviorally in young and middle-aged rats. Rats were lesioned at either 3 or 17 months of age by injection of 192 IgG-saporin immunotoxin into the medial septum and the nucleus basalis magnocellularis, and they were then tested on a range of behavioral tasks: a nonmatching-to-position task in a T-maze, an object-recognition task, an object-location task, and an open-field activity test. Depending on the task used, only an age or a lesion effect was observed, but there was no Age X Lesion interaction. Middle-aged and young rats responded to the cholinergic lesions in the same manner. These results show that in the middle-aged rats in which cholinergic transmission was affected, additional injury to the system was not always accompanied by major cognitive dysfunctions.

Acetylcholine↗
PubMed2005

The role of tissue plasminogen activator in methamphetamine-related reward and sensitization.

In the central nervous system, tissue plasminogen activator (tPA) plays a role in synaptic plasticity and remodeling. Our recent study has suggested that tPA participates in the rewarding effects of morphine by regulating dopamine release. In this study, we investigated the role of tPA in methamphetamine (METH)-related reward and sensitization. Repeated METH treatment dose-dependently induced tPA mRNA expression in the frontal cortex, nucleus accumbens, striatum and hippocampus, whereas single METH treatment did not affect tPA mRNA expression in these brain areas. The METH-induced increase in tPA mRNA expression in the nucleus accumbens was completely inhibited by pre-treatment with R(+)-SCH23390 and raclopride, dopamine D1 and D2 receptor antagonists, respectively. In addition, repeated METH treatment increased tPA activity in the nucleus accumbens. There was no difference in METH-induced hyperlocomotion between wild-type and tPA-deficient (tPA-/-) mice. On the other hand, METH-induced conditioned place preference and behavioral sensitization after repeated METH treatment were significantly reduced in tPA-/- mice compared with wild-type mice. The defect of behavioral sensitization in tPA-/- mice was reversed by microinjections of exogenous tPA into the nucleus accumbens. Our findings suggest that tPA is involved in the rewarding effects as well as the sensitization of the locomotor-stimulating effect of METH.

Amphetamine-Related Disorders↗
PubMed2006

Strain specificity and cholinergic modulation of visuospatial attention in three inbred mouse strains.

The tremendous increase in the use of mouse inbred strains and mutant mice to study the molecular basis of psychiatric disorders urges for a better understanding of attentional performance in mice. To this aim, we investigated possible strain differences in performance and cholinergic modulation of visuospatial attention in three widely used mouse inbred strains (129S2/SvHsd, C57BL/6JOlaHsd and DBA/2OlaHsd) in the five-choice serial reaction time task. Results indicated that after extended training, performance of 129S2/SvHsd mice was superior to that of C57BL/6JOlaHsd and DBA/2OlaHsd mice in terms of attention, omission errors, inhibitory control and latencies to correct choice. Increasing the attentional load resulted in comparable decrements in attention in all strains and inhibitory control impairments that were most pronounced in DBA/2OlaHsd mice. Further pharmacological evaluation indicated that all strains showed attentional impairments after treatment with the muscarinic and nicotinic antagonists scopolamine and mecamylamine, respectively. 129S2/SvHsd mice were less sensitive, whereas DBA/2OlaHsd mice appeared more sensitive to the detrimental effects of mecamylamine. In addition, subchronic, but not acute, nicotine treatment slightly improved attentional performance in all strains to the same extent. In conclusion, our data indicate strain specificity with particularly good performance of 129S2/SvHsd mice and strong cholinergic involvement in visuospatial attention in mice.

Animals↗
PubMed2004

Development of an observational instrument to measure mother-infant separation post birth.

The importance of the timing, quality, and quantity of early maternal-infant contact has gained prominence over the years. However, no researcher has adequately documented the nature of maternal-infant contact and separation. This study assessed the psychometric properties of the Index of Mother-Infant Separation (IMIS), pronounced "I miss," which is a 37-item observational measure of the process of mother-infant contact or separation post birth. Assessment of reliability and validity of the IMIS was conducted using data collected in a randomized clinical trial with 224 healthy newborn infants assigned at 1 hour post birth to self-regulatory or routine nursery care (control) groups. Time-sampled observations occurred every 15 minutes. Content validity indices of the IMIS, determined by nine nationally known perinatal experts, were 77% to 100% for instrument items. Construct validity was supported through known-groups hypothesis testing (p < .0001). Interrater reliability was from 86% to 90%. The IMIS is a valid observational measure of maternal contact when raters are trained to score it reliably.

Adult↗
PubMed2003

Altered anxiety-related responses in mutant mice lacking the beta4 subunit of the nicotinic receptor.

Nicotine, acting at nicotinic acetylcholine receptors (nAChRs), is the primary addictive component of tobacco. Smokers often report an anxiolytic effect of cigarettes. This relief of anxiety, attributed to nicotine, is an important contributor to relapse when smokers try to quit. Hence, the study of the anxiolytic effects of nicotine is important for understanding the mechanisms underlying nicotine addiction. Mammalian nAChRs are pentameric ion channels usually composed of alpha andbeta subunits. Taking advantage of beta4-homozygous-null mice (beta4-/-), we examined the role of the nAChR beta4 subunit in anxiety-related behaviors. The beta4-/- mice behaved as though they were less anxious than wild-type littermates on the elevated-plus and staircase mazes, tests that measure anxiety-related behaviors. To obtain an independent, physiological indication of the stress produced by several tests, we measured changes in heart rate using telemetry. Consistently with the behavioral phenotype, beta4-/- mice had a smaller heart rate increase in the elevated-plus maze than did wild-type littermates. In contrast, during social isolation, a separate test for anxiety,beta4-/- mice exhibited a greater increase in heart rate than did wild-type littermates. Finally, beta4-/- mice were indistinguishable from their wild-type littermates in the open field, the light/dark box, and the mirrored chamber. The overall results demonstrate that beta4-containing (beta4*) nAChRs influence behavioral responses during anxiety-related tests, and that this effect depends on the type of anxiety-provoking experience. Through their influence on anxiety-related behavior, beta4* nAChRs might influence both tobacco consumption and smoking relapse.

Animals↗
PubMed1997

Effects of interaural intensity difference on the processing of interaural time difference in the owl's nucleus laminaris.

Interaural time and intensity differences (ITD and IID) are processed independently in the owl's auditory system. This paper examines whether this independence is established in nucleus laminaris (NL), the first site of ITD processing. A plot of discharge rate against time difference (ITD curve) is sinusoidal in NL. The ITDs that produce the peaks are called the most favorable ITDs, and those that produce the troughs are called the least favorable ITDs. IID had little effect on the discharge rates of laminaris neurons for the most and least favorable ITDs. The degree of peak-trough modulation changed slightly with variation in IID. In contrast, IID in tonal stimuli affected the temporal aspect of ITD curves depending on the difference between the stimulus frequency and the neuron's best frequency (BF). For frequencies below BF, IID caused large and systematic shifts in ITD toward the ear in which the sound was louder, whereas for frequencies above BF, IID caused small shifts in ITD toward the opposite ear. IID had little effect on ITD curves taken with BF or broadband noise. These results can be largely accounted for by the effects of frequency and intensity on the timing of impulses at the level of the cochlear nuclei. Thus, the processing of ITD by NL neurons is independent of IID for behaviorally relevant stimuli, because the timing of impulses is insensitive to sound level when the signal is broadband.

Acoustic Stimulation↗