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PubMed2005

Granulocyte colony-stimulating factor induces sensorimotor recovery in intracerebral hemorrhage.

Granulocyte colony-stimulating factor (G-CSF) has been used in the treatment of neutropenia in hematologic disorders. The neuroprotective and anti-inflammatory effects of G-CSF were reported in various neurological disease models. In this study, we examined whether G-CSF induces functional recovery after intracerebral hemorrhage (ICH). ICH was induced using collagenase injection in adult rats. Either G-CSF (50 microg/kg, i.p.) or saline was given from 2 h after ICH and every 24 h for 3 days. 72 h after ICH induction, the rats were sacrificed for histological analysis and measurement of brain edema. Behavioral tests were performed before and 1, 7, 14, 21, 28, and 35 days after ICH. We also measured the blood-brain barrier (BBB) permeability using Evans blue dye injection method. G-CSF-treated rats recovered better on rotarod and limb placing tests, starting from 14 days throughout 5 weeks after ICH. The brain water content and BBB permeability of G-CSF-treated group decreased in the lesioned hemispheres compared with those of ICH-only group. In G-CSF-treated group, the number of TUNEL+, myeloperoxidase+, and OX42+ cells was smaller than that of ICH-only group in the periphery of hematoma. These findings suggest that G-CSF induces long-term sensorimotor recovery after ICH with reduction of brain edema, inflammation, and perihematomal cell death.

Animals↗
PubMed2004

Are age-related deficits in balance performance mediated by time of day in a prosimian primate (Microcebus murinus)?

We examined the effects of age and time of day on balance performance in the gray mouse lemur (Microcebus murinus) in relation to body temperature variations. Groups of young, adult and aged animals were entrained to either short (SP, L/D 10/14) or long photoperiod (LP, L/D 14/10) and tested in the accelerating Rotarod at three phases of their light/dark cycle (beginning and end of the light phase, beginning of the dark phase). In addition, for each test, rectal temperature (Tr) was measured. Under LP, whatever the test phase, this primate showed a clear age-related decrease in balance performance. Under SP, no significant age-related decline in balance could be detected. Whatever the photoperiod, an effect of time of day on balance performance could only be seen in adults, with better performances at the beginning of the dark phase when Tr values were higher. Under LP, daily variations of both balance performance and Tr disappeared with advancing age. Consequently, age differences were substantially greater when testing was conducted during the dark phase of the light/dark cycle. The time of day effect on balance performance and the loss of daily variations with age suggest the influence of age-related changes within the biological clock.

Age Factors↗
PubMed2005

The antinociceptive and anxiolytic-like effects of the metabotropic glutamate receptor 5 (mGluR5) antagonists, MPEP and MTEP, and the mGluR1 antagonist, LY456236, in rodents: a comparison of efficacy and side-effect profiles.

RATIONALE: Modulation of metabotropic glutamate receptor (mGluR) subtypes represents a novel approach for the treatment of neurological and psychiatric disorders. OBJECTIVES: This study was conducted to investigate the role of the mGluR5 and mGluR1 subtypes in the modulation of pain and anxiety. METHODS: The mGluR5 antagonists, 2-methyl-6-(phenylethynyl)pyridine (MPEP) and 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP), and the mGluR1 antagonist, (4-methoxy-phenyl)-(6-methoxy-quinazolin-4-yl)-amine HCl (LY456236), were tested in models of pain [mouse formalin test, rat spinal nerve ligation (SNL)] and anxiety [Vogel conflict, conditioned lick suppression (CLS)], and their efficacious effects were compared to any associated side effects. RESULTS: The systemic administration of MPEP, MTEP, and LY456236 reduced hyperalgesia induced by formalin and mechanical allodynia following SNL. However, only LY456236 completely reversed the allodynia. In the anxiety models, MPEP (3--30 mg/kg), MTEP (3--10 mg/kg), and LY456236 (10--30 mg/kg) produced anxiolytic-like effects similar to the benzodiazepine, chlordiazepoxide (CDP, 6 mg/kg). However, only MPEP and MTEP were able to produce a level of anxiolysis comparable to CDP. In a series of tests examining potential side effects, MPEP and MTEP reduced body temperature and locomotor activity and impaired operant responding for food and rotarod performance at doses of 3--30 and 1--30 mg/kg, respectively. LY456236 reduced operant responding at 30 mg/kg. CONCLUSION: Both mGluR5 and mGluR1 antagonists are effective in models of pain and anxiety. However, an mGluR1 antagonist was more efficacious than the two mGluR5 antagonists in the pain models, which, conversely, appeared more efficacious in the anxiety models. These findings support the potential utility of mGluR5 and mGluR1 antagonists for both the treatment of chronic pain and as novel anxiolytics.

Analgesics↗
PubMed2005

No phenotype associated with established lipopolysaccharide model for cerebral palsy.

OBJECTIVE: Cerebral palsy (CP) is associated with childhood spasticity, seizures, and paralysis. Oligodendrocyte damage resulting in periventicular leukomalacia (PVL) in the developing brain has been implicated. Animal models of CP have used prenatal hypoxia and infection with histopathology of PVL as the end point. To evaluate whether this histologic end point is associated with a CP phenotype, we reproduced a lipopolysaccharide (LPS) model for PVL, 1 and evaluated developmental, behavioral, and motor outcomes. STUDY DESIGN: On gestational day 15, Fischer 344 rats were intracervically injected with .1 mg/kg LPS (n = 5) or saline (n = 4). After delivery, evaluation for developmental milestones was performed on days 1 to 21 (LPS = 45; control = 30 pups). Males were also tested at 2.5 months using open-field, rotarod, and anxiety tests. On day 21, 2 pups/litter were perfused for immunohistochemistry, and stained with 2 oligodendrocyte antibodies: 2', d'-cyclic nucleotide phosphodiesterase (CNP), and myelin proteolipid protein (PLP) with relative densities of staining assessed using NIH Image software. Statistical analysis included Mann-Whitney U and analysis of variance (ANOVA). RESULTS: LPS pups demonstrated decreased CNP (P = .04) and PLP (P = .06) staining, replicating the model. There was no difference seen in neonatal weight, righting, negative geotaxis, cliff aversion, rooting, forelimb grasp, audio startle, air righting, eye opening, and activity. Surprisingly, LPS-exposed neonatal rats mastered forelimb placement (P < .01) and surface righting (P = .02) earlier than control rats. There were no differences between adult groups in open field distance traveled (P = .8), open-field locomotion time (P = .6), rotarod (P = .6), or anxiety (P = .7). CONCLUSION: Histologic evidence of white matter damage can be replicated using an LPS model for intrauterine inflammation. Significant phenotypic differences consistent with the motor and cognitive damage sequelae of such lesions (ie, CP) were not demonstrated. When evaluating animal models, it is important to assess not only biochemical markers for human disease, but also clinically relevant phenotypes.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed2002

Dopamine-receptor stimulation in the prefrontal cortex ameliorates stress-induced rotarod impairment.

Exposure to chronic stress is thought to play an important role in the etiology of depression. In this disorder, dopaminergic dysfunction in the prefrontal cortex (PFC) is thought to be involved. Indeed, chronic stress reduces dopaminergic transmission in the rat PFC or induces a behaviorally depressive state. However, a relationship between the reduced dopaminergic activity and the behavior of the chronically stressed rats has not been proven. Here, we examined the effects of local application of a dopamine Type I (D(1)) receptor-specific agonist, SKF 81297, in the PFC on the chronic-stress-induced depressive state using a rotarod test. The chronic stress produced by water immersion and restraint for 4 weeks followed by recovery for 10 days impaired the rotarod performance without changing the traction performance or locomotor activity. Although intra-PFC infusion of 1 or 10 ng of SKF 81297 did not affect this impairment, 100 ng of SKF 81297 significantly ameliorated it. These results suggest that the chronic-stress-induced depressive state is caused by a D(1) receptor-mediated hypodopaminergic mechanism in the PFC. These findings will further understanding of the mechanisms underlying the pathophysiology of depression.

Animals↗
PubMed1980

[Development of behavioral function of cerebellar hypoplasia rats as induced by cytosine arabinoside (ara-C) (author's transl)].

Cytosine arabinoside (ara-C), an antiproliferative agent, was given subcutaneously to Sprague-Dawley rats on the 2-4th postnatal day in doses of 12.5 and 25 mg/kg/day. Body weight and viability were found to be dose-dependently inhibited. The appearance of audio-startle response was delayed in the group on the high dose and up to 21 days of age, the ambulatory behavior resembled that seen in geriatric rats. The free-fall righting reflex failed to appear in the treated groups. The open field test revealed that only the treated females were hypoactive. The treated group showed a poor neuro-muscular ability in the rotarod performance and impairment of acquiring conditioned and unconditioned avoidance response in pole climbing. Histopathological and biochemical studies revealed a hypoplasia of the cerebellum. These findings are suggestive of behavioral dysfunction caused by ara-C-induced cerebellar disorders.

Animals↗
PubMed2005

[Pharmacological profiles of benzodiazepinergic hypnotics and correlations with receptor subtypes].

We examined the behavioral pharmacological properties of six benzodiazepine (omega) receptor ligands including brotizoram, nitrazepam, quazepam, rilmazafone, zolpidem and zopiclone and the binding of these drugs with omega receptor subtypes. Behavioral tests were performed at the time of the maximal effects induced by each drug following its oral administration to mice. All of these drugs dose-dependently induced impairment of motor coordination as rotarod performance and potentiation of thiopental-induced anesthesia as hypnotic effect. The hypnotic effects of rilmazafone, whose major metabolites were bound to both omega1 and omega2 receptors with high affinity, and omega1 selective quazepam were about 20 times more effective than the induction of motor impairments when compared with ED50 values. However, there was no difference between the ED50 values of omega1 selective zolpidem alone in these two tests. An antianxiety efficacy of zolpidem was relatively weak unlike that of other drugs in the elevated plus-maze. It has been reported that omega2, but not omega1, receptors are associated with motor impairment and anxiolytic effect. The weak anxiolytic effect of zolpidem supports the previous hypothesis. However, the strong motor incoordination of zolpidem suggests that not only omega2 but also omega1 receptors are related to motor impairment unlike the previous hypothesis.

Animals↗
PubMed2007

Developmental exposure to methylmercury alters learning and induces depression-like behavior in male mice.

To investigate the long-term effects of developmental exposure to methylmercury (MeHg), pregnant mice were exposed to at 0.5 mg MeHg/kg/day via drinking water from gestational day 7 until day 7 after delivery. The behavior of offspring was monitored at 5-15 and 26-36 weeks of age using an automated system (IntelliCage) designed for continuous long-term recording of the home cage behavior in social groups and complex analysis of basic activities and learning. In addition, spontaneous locomotion, motor coordination on the accelerating rotarod, spatial learning in Morris water maze, and depression-like behavior in forced swimming test were also studied. The analysis of behavior performed in the IntelliCage without social deprivation occurred to be more sensitive in detecting alterations in activity and learning paradigms. We found normal motor function but decreased exploratory activity in MeHg-exposed male mice, especially at young age. Learning disturbances observed in MeHg-exposed male animals suggest reference memory impairment. Interestingly, the forced swimming test revealed a predisposition to depressive-like behavior in the MeHg-exposed male offspring. This study provides novel evidence that the developmental exposure to MeHg can affect not only cognitive functions but also motivation-driven behaviors.

Alkaline Phosphatase↗
PubMed2005

Scheduled access to ethanol results in motor impairment and tolerance in female C57BL/6J mice.

We recently reported a method where water-restricted mice were given scheduled access to ethanol followed by access to water. C57BL/6J mice would repeatedly self-administer ethanol in amounts that produced high and stable blood ethanol concentrations (BEC) [Finn DA, Belknap JK, Cronise K, Yoneyama N, Murillo A, Crabbe JC. A procedure to produce high alcohol intake in mice. Psychopharmacol 2005;178:471-480]. The studies reported here demonstrate that behavioral signs of motor impairment result from these high alcohol intakes, and that there was some evidence of tolerance development across repeated sessions. Female C57BL/6J mice were allowed 30 min access to ethanol (5% v/v) followed by 2.5 h access to water either: every 3rd day for 12 days; every 2nd day for 28 days; or every 2nd day for 9 days. On intervening days, mice had 3 h access to water. A control group had daily access to water only. Mice consumed 2-2.5 g/kg ethanol in 30 min, resulting in BECs of 1.4-1.5 mg/ml. Motor impairment was assessed using the accelerating or fixed speed rotarod, balance beam or screen test. In all studies, mice were tested for motor impairment immediately after 30 min access to ethanol or water. In Experiment 1, ethanol-exposed mice had shorter latencies to fall from the fixed speed rotarod and more foot slips on the balance beam than the control group, indicating motor impairment. After drinking ethanol, mice also fell from a screen more quickly than during sober pretraining. In Experiment 2, mice tested (without prior training) for motor impairment and tolerance on the fixed speed rotarod at 6.5 and 10 RPM showed repeated motor impairment in the ethanol group, but did not develop tolerance. In Experiment 3, mice were first given rotarod training at 10 RPM. Following each fluid access period, performance was impaired in mice self-administering ethanol at 10, but not 15 RPM, when compared to control mice. There was no evidence of tolerance across days. However, on the last day, all mice were tested at both RPM following an i.p. injection of 2 g/kg ethanol. Ethanol-experienced mice were less impaired at both RPM than the ethanol-naïve mice, indicating tolerance development according to this between-groups index. These results suggest that C57BL/6J mice will repeatedly consume alcohol in amounts that produce motor impairment under these scheduled fluid access conditions, and that a modest degree of tolerance can be detected using appropriate tests.

Alcohol Drinking↗
PubMed2002

Environmental enrichment slows disease progression in R6/2 Huntington's disease mice.

Huntington's disease is a genetic disorder that causes motor dysfunction, personality changes, dementia, and premature death. There is currently no effective therapy. Several transgenic models of Huntington's disease are available, the most widely used of which is the R6/2 mouse, because of its rapid disease progression. Environmental enrichment alters gene expression in the normal mouse brain, and modulates the course of several neurological disorders. Environmentally enriched mice may actually mimic human disease more accurately. We found that even limited environmental enrichment slows decline in RotaRod performance in R6/2 mice, despite rapid disease progression, whereas in normal littermates, maximal enrichment was required to induce a marked improvement in behavioral tests. Enrichment also delayed the loss of peristriatal cerebral volume in R6/2 brains. These results could provide the basis for a rational approach to ameliorate the effects of Huntington's disease.

Animals↗
PubMed2004

Effects of riluzole on combined MPTP + 3-nitropropionic acid-induced mild to moderate striatonigral degeneration in mice.

We investigated the potency of riluzole, an anti-glutamatergic drug, to affect ongoing neuronal death process following combined MPTP + 3-nitropropionic acid (3-NP) intoxication producing combined striatal and nigral degeneration (SND) in mice. We used a "neuronal rescue" strategy by administering riluzole after the end of intoxication. The motor disorder, its recovery, behavioral performances at motor and sensorimotor integration tasks and histopathological outcome were compared in the saline and riluzole groups (10 mg/kg and 20 mg/kg), matched by triplets for motor severity. While riluzole did not produce any effect on the gross motor disorder nor on rotarod task, open-field kinetic variables or on the traversing beam task, it had a subtle effect on the performances at the pole test. The histopathological outcome was significantly better in the riluzole-treated mice regarding both nigral and dorsolateral striatal cell loss and astroglial activation, with a dose-effect relationship. Thus, riluzole has limited "neuronal rescue" properties from an histopathological point of view with a subtle motor behavior improvement in a MPTP + 3-NP-induced SND in mice.

Animals↗
PubMed1977

[Behavioral effects of 5-(o-chlorophenyl)-1-methyl-7-nitro-1,3-dihydro-2H-1,4-benzodiazepin-2-one (ID-690)].

Effects on the central nervous system of ID-690, a new benzodiazepine derivative were investigated and compared mainly with those of diazepam in mice and rats. Locomotor activity of the rat was increased with ID-690, at doses of 2 approximately 5 mg/kg p.o., as with diazepam. ID-690 was approximately 5 times more potent than diazepam in inhibiting fighting behavior of long-term isolated mice. Hyperemotionality induced by either septal lesions or olfactory bulbectomy was also inhibited by ID-690. This effect was almost the same in potency as that of diazepam. ID-690 was only 1/30 as potent as diazepam in preventing maximal electroshock convulsion, while it was approximately 18 times more potent that diazepam in suppressing pentetrazol convulsion in mice. ID-690 was approximately 5 times as potent as diazepam in impairing rotarod performance in mice. The muscle relaxant effect of ID-690 was approximately 10 times as potent as diazepam, as measured with an inclined screen test in mice. Thus the effect of ID-690, as compared with diazepam, was characterized by its relatively potent muscle relaxant and extremely potent anti-pentetrazol convulsant action.

Agonistic Behavior↗
PubMedDate not supplied

Long-term deficits in cerebellar growth and rotarod performance of rats following "binge-like" alcohol exposure during the neonatal brain growth spurt.

The cerebellum is vulnerable to growth restriction and neuronal depletion induced by alcohol exposure during the brain growth spurt of neonatal rats. This study examined whether neonatal alcohol exposure permanently restricted brain growth and induced motor performance deficits in adults. Two groups of rats were given 4.5 g/kg of alcohol per day during postnatal days 4 through 9, using artificial-rearing procedures. One group was given the alcohol as a 10.2% (v/v) solution in two of the 12 daily feedings, producing peak BACs of 361 mg/dl. The second group was given the alcohol as a 5.1% (v/v) solution in four of the feedings, producing peak BACs of 187 mg/dl. Controls included an artificially reared group and a normally reared group. All rats were tested on a rotarod at approximately 405 days of age, then perfused 1-2 weeks later. The 10.2% group was significantly impaired in acquiring the task and had significant reductions in whole brain and cerebellar weight, compared to controls. The 5.1% treatment also significantly restricted whole brain and cerebellar growth, and rotarod performance of that group was intermediate between the control groups and the 10.2% group. The cerebellar reductions and deficits in motor performance in adulthood demonstrate permanent structural and functional consequences of binge-like alcohol exposure during the brain growth spurt.

Animals↗
PubMed2003

Neurobehavioral effects of alcohol in AMPA receptor subunit (GluR1) deficient mice.

Of the ionotropic glutamatergic receptors, the NMDA receptor is clearly implicated in the acute and chronic effects of ethanol; however, the role of the AMPA receptor in mediating the effects of ethanol in vivo is as yet unclear. Using mice deficient in the AMPA receptor subunit GluR1 (GluR1-/- mice), we investigated whether the AMPA receptor had a significant role in mediating the effects of ethanol. GluR1-/- mice showed greater locomotor activity in a novel environment, but by the fifth day of repeated testing their activity was the same as that of wild-type mice. In contrast to their enhanced locomotor activity, on an accelerating rotarod GluR1-/- mice performed consistently worse than wild-types. With regard to the effects of ethanol on motor responses, GluR1-/- mice did not differ significantly from wild-type mice in ethanol's sedative or incoordinating effects. However, the GluR1-/- mice were insensitive to the hypothermic effects of a hypnotic dose of ethanol in contrast to wild-types; this effect was dissociable from the hypnotic effects of ethanol. Further, tolerance to ethanol developed equally for GluR1-/- mice versus wild-type mice. In terms of alcohol drinking behavior, compared to wild-types, GluR1-/- mice differed neither in the acquisition of voluntary ethanol consumption nor in stress-induced ethanol drinking, nor in the expression of an alcohol deprivation effect (ADE) which is used as a model of relapse-like drinking behavior. In summary, although the loss of a hypothermic effect of ethanol in GluR1-/- mice indicates a critical role for the AMPA receptors in this effect, the GluR1 subunit of the AMPA receptor does not seem to play a critical role in the etiology of alcohol dependence. However, changes observed in activity patterns may be related to the putative role of AMPA receptors in attention deficit hyperactivity disorder.

Alcohol Drinking↗
PubMed2002

Estradiol protects against cerebellar damage and motor deficit in ethanol-withdrawn rats.

On the basis of findings obtained from this study, we hypothesize that the female sex steroid 17beta-estradiol (E(2)) protects against cerebellar neuronal damage and behavioral deficit in rats withdrawn from chronic ethanol exposure. Ovariectomized rats implanted with E(2) or an oil pellet received liquid ethanol (7.5% [wt./vol.]) or dextrin diet for 5 weeks, followed by 2 weeks of ethanol withdrawal. On termination of diet administration, rats were tested for both overt withdrawal signs and latency (seconds) to fall from an accelerating rotarod in six consecutive sessions (the longer the latency, the better the performance). The initial latency was measured separately to assess motoric capacity before learning occurred. Rats were then killed, and cerebella were prepared for accessing of Purkinje cell damage. The study revealed three specific findings. (1) In the absence of E(2), the ethanol withdrawal group showed higher total ethanol withdrawal sign scores than those for the dextrin group, whereas the score for the ethanol withdrawal group was lower in the presence of E(2). (2) In the absence of E(2), the ethanol withdrawal group showed shorter rotarod latency than that for the dextrin group, whereas the latency for the ethanol withdrawal group increased in the E(2)-treated group. In ethanol withdrawal groups, E(2) treatment also resulted in a longer latency than that observed with oil treatment in the initial session and in subsequent sessions. (3) Purkinje cell numbers in the ethanol withdrawal group without E(2) were lower than those in dextrin groups and in the ethanol withdrawal group with E(2) treatment. These findings support the suggestion that E(2) exerts protective effects against withdrawal signs, cerebellar neuronal damage, and motoric impairment in subjects exposed to, and withdrawn from, chronic ethanol exposure.

Animals↗
PubMed1991

Assessment of acute behavioral toxicity of low doses of diisopropylfluorophosphate (DFP) in rats.

The effect on behavior of single subtoxic doses (100 and 600 micrograms/kg i.p., i.e. 1/77 and 1/13 of LD50, respectively) of an organophosphorous compound, diisopropylfluorophosphate (DFP), was studied in male Wistar rats. In the open-field test, the lower dose of DFP tended to increase ambulation, while the higher dose showed a trend towards a decrease in ambulation, rearing and frequency of defecation. In the elevated plus-maze, rotarod, elevated bridges and hot plate tests, DFP-treated rats did not differ significantly from the olive oil-treated controls. DFP significantly impaired the performance of rats in the one-trial passive avoidance task and dose-dependently decreased spontaneous locomotor activity for 4 hours after administration. At the doses used DFP only slightly inhibited acetylcholinesterase activity in the blood and different brain areas. The results show that the higher dose of DFP had an inactivating effect on the behavior of rats, while the lower dose did not markedly change their behavioral pattern. Our findings indicate that anticholinesterase compounds, such as DFP, can alter behavior even after single small subtoxic doses.

Acetylcholinesterase↗
PubMed1999

Comparison of the pharmacological properties of classical and novel BZ-omega receptor ligands.

The experiments in this study compared the pharmacological properties of several BZ-omega receptor ligands, including the imidazobenzodiazepine imidazenil, the beta-carboline abecarnil, the pyridazinone Y-23684, the pyrido [1,2-a]benzimidazole RWJ 46771 and the 1,6-naphthyridin-2(1H)-one derivative SX-3228, with the prototypical BZs diazepam, clobazam and bretazenil. In in vitro experiments diazepam, bretazenil, imidazenil and Y-23684 displaced [3H]flumazenil binding non-selectively in membranes from rat cerebellum and spinal cord, two brain areas enriched in the BZ-omega 1 and BZ-omega 2 receptor subtypes, respectively. In contrast, abecarnil, RWJ 46771 and SX-3228 were more potent in displacing [3H]flumazenil binding to membranes from rat cerebellum than from spinal cord or hippocampus, indicating selectivity for the BZ-omega 1 receptor subtype. The in vivo experiments showed that all compounds increased the latency to clonic seizures produced by isoniazid. However, the maximal increase in latency induced by diazepam, clobazam, abecarnil, RWJ 46771 and SX-3228 was greater than that of bretazenil, imidazenil and Y-23684, thereby indicating that these latter compounds have low intrinsic efficacy. In the punished drinking, the punished lever pressing and the elevated plus-maze tests in rats, three models of anxiety, diazepam, clobazam and imidazenil elicited clear anxiolytic-like effects but at doses which were close to those producing hypolocomotion, ataxia and myorelaxation as measured in activity cages, the rotarod and the loaded grid tests, respectively. In contrast, bretazenil and Y-23684 induced anxiolytic-like activity at much lower doses than those which impaired motor performances. The magnitude of the positive effects of Y-23684 was similar to that of the reference BZs, suggesting that it may become a valuable alternative to currently used agents for the treatment of anxiety disorders. Abecarnil, RWJ 46771 and SX-3228 produced weaker or non-specific anxiolytic-like effects as they decreased anxiety-related behaviours at doses similar or close to those impairing motor performance. However, unlike the other compounds they induced myorelaxation at doses which were 3-10 times higher than those needed to produce decrease in exploratory activity. It is suggested that the behavioural profiles of abecarnil, RWJ 46771 and SX-3228 may be attributed to their selectivity for the BZ-omega 1 receptor subtype which may account for their sedative activity, thereby masking other effects including anxiolytic-like activity. This suggests that BZ receptor modulation of anxiety may involve BZ receptor subtypes other than BZ-omega 1.

Animals↗
PubMed1999

Brain free magnesium concentration is predictive of motor outcome following traumatic axonal brain injury in rats.

A number of studies have supported a role for brain free magnesium as an important secondary injury factor in the development of neurologic deficits following traumatic brain injury. Despite this, few studies have characterised free magnesium changes in diffuse models of brain injury relevant to clinical trauma, and none have critically examined the association between brain free magnesium concentration and degree of neurologic deficit following graded trauma. In the present study, a combination of nuclear magnetic resonance spectroscopy and rotarod motor function tests were used to characterise the relationship between brain free magnesium concentration and neurologic motor function following graded traumatic axonal brain injury in rats. Induction of moderate or severe impact-acceleration induced traumatic brain injury resulted in a profound decline (p < 0.01) in brain free magnesium concentration that persisted for a minimum of 4 days post-trauma in both injury groups. Posttraumatic rotarod deficits assessed on a daily basis after injury were linearly correlated with brain free magnesium concentration measured in the same animals immediately after the motor tests were performed (r = 0.87; p < 0.001). These results suggest that brain free magnesium declines following graded diffuse axonal brain injury and that the concentration of the ion after trauma may be a prognostic indicator of motor outcome following.

Animals↗