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PubMed2004

Behavioural profiles of inbred mouse strains used as transgenic backgrounds. I: motor tests.

One of the characteristic manifestations in several neurodegenarative diseases is the loss of voluntary motor control and the development of involuntary movements. In order to determine the suitability of six mouse strains as transgenic background strains we investigated performance on a variety of tasks designed to identify subtle changes in motor control. On both the accelerating and the staggered speed rotarod all six mouse strains performed well. However, latency to fall from the rod was sensitive to both rotarod speed and repeated exposure to the apparatus. Performance of the DBA/2 mouse strain was highly variable across the time points used. On the acoustic startle test CBA mice showed the greatest degree of reactivity to the acoustic startle stimuli with both the C57 and DBA showing the least. Complex strain differences were also identified on measures of habituation to the startle stimuli and variations in the prepulse noise level, and prepulse/startle delay. Gait analysis using the footprint test did not reveal strain differences on measures of base width, overlap or stride length but the 129S2/Sv strain took significantly longer to traverse the runway than the other mouse strains. Finally, the swim tank test detected complex strain differences in swim speed, and the number of fore- and hindpaw paddles required to swim the length of the tank. These data taken together suggest that choice of background strain is a crucial consideration for the repeated behavioural assessment of motor deficits in transgenic mouse models of disease.

Acoustic Stimulation↗
PubMed1989

Effects of subacute administration of physostigmine on blood acetylcholinesterase activity, motor performance, and soman intoxication.

Subacute administration of carbamates is under study as pretreatment against soman, a toxic anticholinesterase agent. In this study, the sustained release of physostigmine salicylate (Phy) in rats was achieved via osmotic minipumps; each pump contained 2 ml of Phy solution (0.4, 10, or 50 mg/ml) and delivered 2.5 microliter/hr for 28 days. At the corresponding dosage rates, rat whole blood acetylcholinesterase (AChE) activity was suppressed by approximately 11, 42, and 66%, respectively. These levels of Phy administration caused no decrement in performance on an accelerating rotarod (ARR) when tested between Days 3 and 27 of the 28-day exposure. The highest level of Phy caused a mean weight loss of 11% initially, with recovery by the 17th day. On Day 27 the rats were given 0.08 mg/kg, im, of scopolamine (SCP), 30 min before exposure to soman (58 micrograms/kg; 1 LD50, iv). In combination with SCP, the two highest levels of Phy prevented lethality and a decrement in ARR performance by soman, while the lowest level showed 40% lethality after soman and the survivors exhibited partial recovery to their own presoman control performance by 24 hr. These results suggest that, in a pretreatment mode, 42-66% inhibition of AChE by sustained exposure to Phy, with an acute dose of cholinolytic, would suffice to protect against lethality and motor performance decrement by a toxic level of soman.

Acetylcholinesterase↗
PubMed1999

Effects of four herbal extracts on adjuvant-induced inflammation and hyperalgesia in rats.

OBJECTIVE: To evaluate the effects of four herbal medicine extracts on a rat model of inflammatory hyperalgesia. DESIGN/INTERVENTIONS: Inflammation was induced by injecting complete Freund's adjuvant (CFA) into one hindpaw of each rat. Four herbs that are routinely prescribed in Traditional Chinese Medicine for treatment of pain were used: Duhuo (Radix Angelicae Pubescentis), Bai jiang cao (Patriniae Herba cum Radice), Yan hu suo (Rhizoma Corydalis) and Sanqui (Panax Notoginseng). The crude water extracts of the herbs were inected intraperitoneally following a repeated treatment profile. OUTCOME MEASURES: Thermal hyperalgesia was assessed by testing each rat's paw withdrawal response to a noxious thermal stimulus. The magnitude of edema was determined by measuring the maximal thickness of the paw with a caliper. The effect of herb extracts on motor performance was assessed by using an accelerating rotarod test. RESULT: Duhuo, Bai jiang cao, and Yan hu suo significantly attenuated CFA-induced hyperalgesia at 2 hours and facilitated the recovery from hyperalgesia (p < 0.05), when compared to saline-treated rats. The CFA-induced edema was reduced by Duhuo at 24 hours, 72 hours and 168 hours; Bai jiang cao at 24 hours, and Yan hu suo at 24 hours and 168 hours. Sanqi did not produce any significant effect on inflammation and hyperalgesia. The rotarod performance was slightly reduced by Bai jiang cao, Yan hu suo, and Sanqi (p < 0.05) but not by Duhuo treatment. CONCLUSION: The present study identified Duhuo as a selective and effective herbal agent in attenuating persistent hindpaw inflammation and hyperalgesia in rats. These results indicate that some herbal agents may provide an alternative approach to the treatment of persistant inflammatory pain and hyperalgesia.

Animals↗
PubMed2003

Influence of CGS 21680, a selective adenosine A(2A) agonist, on the phencyclidine-induced sensorimotor gating deficit and motor behaviour in rats.

RATIONALE: Recently it has been suggested that adenosine A(2A) receptor agonists may be potential antipsychotic drugs. It is, however, not clear whether these compounds may exert their antipsychotic effect without producing extrapyramidal side-effects (e.g. catalepsy, muscle rigidity, ataxia). It is known that such side-effects may be due to overactivation of the GABAergic strio-pallidal pathway, which may be estimated as an increased expression of proenkephalin (PENK) mRNA in the striatum. OBJECTIVE: The aim of this study was to determine whether CGS 21680, a selective adenosine A(2A) receptor agonist, can reverse the disruption of prepulse inhibition (PPI) of the acoustic startle response induced by the non-competitive antagonist of NMDA receptors phencyclidine (PCP) without producing motor side-effects in rats. RESULTS: Systemic administration of PCP (5 mg/kg) produced profound reduction of the PPI, which was reversed by CGS 21680 (1 mg/kg). CGS 21680 (0.1 and 1 mg/kg) was without effect on catalepsy, muscle rigidity and rotarod performance in rats as well as on the PENK mRNA expression in the striatum estimated by in situ hybridization. Only after the highest dose used (5 mg/kg) were signs of catalepsy (measured using a 9-cm cork test), disturbed balance and a loss of hind limb control (measured in the rotarod test) seen. Moreover, increased muscle resistance during passive extension measured mechanomyographically after this dose of CGS 21680 was observed. CONCLUSIONS: The present results support the hypothesis that adenosine A(2A) receptor agonists may be potentially useful antipsychotic agents with the low incidence of extrapyramidal side-effects.

Adenosine↗
PubMed1994

Effects of acute combined inhalation exposure to n-butyl alcohol and n-butyl acetate in experimental animals.

The effects of combined exposure to n-butyl alcohol and n-butyl acetate on rotarod performance and hot plate behaviour in rats and respiratory rate in mice were investigated in the condition of an acute inhalation experiment. Rotarod performance and hot-plate behaviour were tested in rats exposed to various concentrations of n-butyl alcohol, n-butyl acetate and their mixture consisting of 50 Vol-% n-butyl alcohol and 50 Vol-% n-butyl acetate immediately after termination of a 4-hour exposure period. The respiratory rate in mice was recorded continuously before the exposure to solvents, during 6 min of exposure and 6 min after termination of exposure using whole body plethysmographic method. Mice were exposed to vapours of single solvents and their 50:50 Vol-% mixture. Both solvents and their mixture caused concentration-dependent disturbances of rotarod performance in rat. The medial effective concentration (EC50) for the effect amounted to 7559 ppm, 8339 ppm and 10672 ppm for n-butyl alcohol, n-butyl acetate and their mixture, respectively. Both solvents and their mixture decreased sensitivity to the pain and changes were concentration-dependent. In condition of combined exposure the results obtained in rotarod and hot-plate behaviour test indicate the summation of individual solvent effects. The tested solvents resulted in concentration-dependent decrease in respiratory rate in mice. n-Butyl alcohol produced maximal decrease in respiratory rate in the first minute of exposure whereas n-butyl acetate in the sixth minute.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Butanol↗
PubMed2006

Deletion of the triplet repeat encoding polyglutamine within the mouse Huntington's disease gene results in subtle behavioral/motor phenotypes in vivo and elevated levels of ATP with cellular senescence in vitro.

Huntingtin (htt), the protein encoded by the Huntington's disease (HD) gene, contains a polymorphic stretch of glutamines (polyQ) near its N-terminus. When the polyQ stretch is expanded beyond 37Q, HD results. However, the role of the normal polyQ stretch in the function of htt is still unknown. To determine the contribution of the polyQ stretch to normal htt function, we have generated mice with a precise deletion of the short CAG triplet repeat encoding 7Q in the mouse HD gene (Hdh(DeltaQ)). Hdh(DeltaQ/DeltaQ) mice are born with normal Mendelian frequency and exhibit no gross phenotypic differences in comparison to control littermates, suggesting that the polyQ stretch is not essential for htt's functions during embryonic development. Adult mice, however, commit more errors initially in the Barnes circular maze learning and memory test and perform slightly better than wild-type controls in the accelerating rotarod test for motor coordination. To determine whether these phenotypes may reflect an altered cellular physiology in the Hdh(DeltaQ) mice, we characterized the growth and energy status of primary embryonic and adult Hdh(DeltaQ/DeltaQ) fibroblasts in culture. The Hdh(DeltaQ) fibroblasts exhibited elevated levels of ATP, but senesced prematurely in comparison with wild-type fibroblasts. Taken altogether, these results suggest that htt's polyQ stretch is required for modulating longevity in culture and support the hypothesis that the polyQ stretch may also modulate a htt function involved in regulating energy homeostasis.

Adenosine Triphosphate↗
PubMed1991

Treatment with methylazoxymethanol at different gestational days: physical, reflex development and spontaneous activity in the offspring.

Pregnant rats were injected with a single dose of methylazoxymethanol (MAM, 25 mg/kg) on gestational day 14, 15, 16, 17, 18 or 19 and offspring were tested for their physical development, reflex development and spontaneous activity. MAM treatment did not affect gestational and litter parameters at any of the time of administration studied. Treatment at gestational day 14 (GD14) had the most severe effect on functional neurodevelopment until weaning: righting reflex at surface, chimney test, horizontal wire test resulted altered. Administration at GD15, 16, 18, 19 did not affect the performance in these tests. Offspring treated at GD17 showed a delayed eye opening and an impaired performance in the horizontal wire test. When tested at 50 days of age on the rotarod, all the treated groups performed worse than controls with the exception of GD19 treated offspring. Administration at GD14 and GD15 resulted in increased spontaneous activity of the offspring at 21 days but not at 60 days of age. Different degrees of microencephaly were observed for all treated groups. The results indicate that alterations of physical and behavioral development induced by MAM treatment are dependent on the time of MAM administration, and specific behavioral tests are able to detect different abnormalities and differentiate among treatment groups. Some alterations observed in MAM rats undergo to adaptive changes during maturation of the CNS.

Animals↗
PubMed2004

Evidence of the antiepileptic potential of amiloride with neuropharmacological benefits in rodent models of epilepsy and behavior.

Sodium-hydrogen exchangers (NHEs) in the brain play a key role in regulating neuronal pH and, hence, modulate bioelectric and seizure activity. In this study, we investigated the anticonvulsant effect of amiloride (a NHE inhibitor) on increasing current electroshock (ICES) and pentylenetetrazole (PTZ)-induced seizures in mice. Further, the effect of amiloride on mood, memory, grip strength, and rotarod performance was also evaluated. The forced swimming test (FST) and spontaneous alternation behavior (SAB) models were employed to assess the effects on mood and memory, respectively. Amiloride produced a dose-dependent increase in seizure threshold in both rodent models of epilepsy. It was observed that amiloride reduced behavioral depression in the FST in mice. In addition, it resulted in memory improvement in the SAB model. Amiloride did not affect grip strength and rotarod performance, suggesting it is devoid of behavioral impairment. The results indicate the potential antiseizure activity of amiloride along with additional neurological advantages.

Amiloride↗
PubMed2006

The stairway: a novel behavioral test detecting sensomotoric stroke deficits in rats.

New therapeutic concepts of cell and tissue replacement therapies have been introduced in treatment of neurological disorders which require robust and sensitive sensomotoric behavioral diagnostic test systems for experimental research. However, most test arrays available are either expensive and/or sensitive to environmental disturbances. Moreover, an extensive training phase for experimental animals is often required by conventional tests to get reproducible data. In this study, we describe a new test array, the Stairway, that is robust, cost-effective, and needs only a minimum training phase. Its efficiency is evaluated in comparison to the well-established RotaRod and modified neurological severity score. Stroke was induced by middle cerebral artery occlusion. Human umbilical cord blood transplantation (n = 18) was performed 24 h after stroke by intravenous injection of suspended cells in comparison to control injections (n = 18), while behavioral assessment was carried out continuously for 29 days. Furthermore, development of lesions was monitored by magnetic resonance imaging. The results reveal the Stairway test as a simple, highly reproducible, and easy manageable test system thus reflecting therapeutic benefits precisely.

Animals↗
PubMed2002

Postischemic administration of basic fibroblast growth factor improves sensorimotor function and reduces infarct size following permanent focal cerebral ischemia in the rat.

Basic fibroblast growth factor (bFGF) is a polypeptide with potent trophic and protective effects on the brain. bFGF has been reported to exert neuroprotection against a wide variety of insults, including ischemic neuronal injury. To date, animal models of focal ischemia have not been translated to efficacy in stroke clinically with respect to testing of neuroprotective agents. Because functional outcome is the measurement of efficacy for putative neuroprotective agents in the clinic, we sought to evaluate the functional consequences of bFGF administration in rats subjected to focal ischemia. In this study, we assessed the effects of bFGF on functional outcome as well as infarct size in rats subjected to severe cerebral ischemia by permanent occlusion of the middle cerebral artery (MCAO). Male Sprague-Dawley rats were subjected to permanent MCAO by the intraluminal filament technique. Two hours following occlusion, rats were infused intravenously with either bFGF, at a dose of 150 microg/kg, or vehicle alone. Functional sensorimotor impairment, which was assessed by the accelerating rotarod test, was recorded at baseline and compared to performance assessed at 24 h after MCAO. Permanent occlusion of the MCA caused marked impairment in rotarod performance in both groups. Treatment of rats with bFGF showed a significant 46% improvement in rotarod fall latency when compared with that from the animals treated with vehicle alone. The volume of cortical infarction was significantly reduced by 32% as a function of bFGF treatment. These results suggest that the delayed intravenous administration of bFGF improves sensorimotor function as well as reduces infarct size following permanent focal ischemia in rat.

Animals↗
PubMed2003

Intravenous bone marrow stromal cell therapy reduces apoptosis and promotes endogenous cell proliferation after stroke in female rat.

The present study investigates the induction of neurogenesis, reduction of apoptosis, and promotion of basic fibroblast growth factor (bFGF) expression as possible mechanisms by which treatment of stroke with bone marrow stromal cells (MSCs) improves neurological functional recovery. Additionally, for the first time, we treated cerebral ischemia in female rats with intraveneous administration of MSCs. Female rats were subjected to 2 hr of middle cerebral artery occlusion (MCAo), followed by an injection of 3 x 10(6) male (for Y chromosome labeling) rat MSCs or phosphate-buffered saline (PBS) into the tail vein 24 hr after MCAo. All animals received daily injection of bromodeoxyuridine (BrdU; 50 mg/kg, i.p.) for 13 days after treatment for identification of newly synthesized DNA. Animals were sacrificed at 14 days after MCAo. Behavioral tests (rotarod and adhesive-removal tests) were performed. In situ hybridization, immunohistochemistry, and terminal deoxynucleotidyltransferase (TdT)-mediated dUTP-biotin nick-end labeling (TUNEL) were performed to identify transplanted MSCs (Y chromosome), BrdU, bFGF, and apoptotic cells in the brain. Significant recovery of behavior was found in MSC-treated rats at 7 days in the somatosensory test and at 14 days in the motor test after MCAo compared with control, PBS-treated animals (P<.05). MSCs were found to survive and preferentially localize to the ipsilateral ischemic hemisphere. Significantly more BrdU-positive cells were located in the subventricular zone (P<.05), and significantly fewer apoptotic cells and more bFGF immunoreactive cell were found in the ischemic boundary area (P<.05) of MSC-treated rats than in PBS-treated animals. Here we demonstrate that intravenously administered male MSCs increase bFGF expression, reduce apoptosis, promote endogenous cellular proliferation, and improve functional recovery after stroke in female rats.

Animals↗
PubMedDate not supplied

Effects of prenatal exposure to xylene on postnatal development and behavior in rats.

The effects of prenatal exposure to the organic solvent xylene (dimethylbenzene, CAS-no 1330-20-7) on postnatal development and behavior in rats were studied. Pregnant rats (Mol:WIST) were exposed to 500 ppm technical xylene 6 h per day on gestation days 7-20. The dose level was selected so as not to induce maternal toxicity or decrease the viability of offspring. In the exposed offspring, a delay in the ontogeny of the air righting reflex, a lower absolute brain weight, and impaired performance in behavioral tests for neuromotor abilities (Rotarod) and for learning and memory (Morris water maze) were found. Generally, the effects were most marked in the female offspring.

Animals↗
PubMed2004

Antinociceptive effect of novel pyrazolines in mice.

The antinociceptive effect of six novel synthetic pyrazolines (3-ethoxymethyl-5-ethoxycarbonyl-1H-pyrazole (Pz 1) and its corresponding 1-substituted methyl (Pz 2) and phenyl (Pz 3) analogues, and 3-(1-ethoxyethyl)-5-ethoxycarbonyl-1H-pyrazole (Pz 4) and its corresponding 1-substituted methyl (Pz 5) and phenyl (Pz 6) analogues) was evaluated by the tail immersion test in adult male albino mice. The animals (N = 11-12 in each group) received vehicle (5% Tween 80, 10 ml/kg, sc) or 1.5 mmol/kg of each of the pyrazolines (Pz 1-Pz 6), sc. Fifteen, thirty and sixty minutes after drug administration, the mice were subjected to the tail immersion test. Thirty minutes after drug administration Pz 2 and Pz 3 increased tail withdrawal latency (vehicle = 3.4 +/- 0.2; Pz 2 = 5.2 +/- 0.4; Pz 3 = 5.9 +/- 0.4 s; mean +/- SEM), whereas the other pyrazolines did not present antinociceptive activity. Dose-effect curves (0.15 to 1.5 mmol/kg) were constructed for the bioactive pyrazolines. Pz 2 (1.5 mmol/kg, sc) impaired motor coordination in the rotarod and increased immobility in the open-field test. Pz 3 did not alter rotarod performance and spontaneous locomotion, but increased immobility in the open field at the dose of 1.5 mmol/kg. The involvement of opioid mechanisms in the pyrazoline-induced antinociception was investigated by pretreating the animals with naloxone (2.75 micro mol/kg, sc). Naloxone prevented Pz 3- but not Pz 2-induced antinociception. Moreover, naloxone pretreatment did not alter Pz 3-induced immobility. We conclude that Pz 3-induced antinociception involves opioid mechanisms but this is not the case for Pz 2.

Analgesics↗
PubMed1998

Effects of the competitive N-methyl-D-aspartate antagonist CGP 37849 and its ethylester CGP 39551 on N-methyl-D-aspartate-evoked whole-cell currents in cultured spinal neurones and on vestibular stimulation-induced seizures in EL mice.

The competitive N-methyl-D-aspartate (NMDA) antagonist DL-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CAS 127910-31-0, 4-methyl-APPA, CGP 37849) and its ethyl ester (CAS 127910-32-1, CGP 39551) potently block NMDA-evoked whole-cell current on mouse spinal neurones in primary dissociated cell cultures with IC50 (+/- SE) values of 189 +/- 9 nmol/l (CGP 37849) and 2100 +/- 220 nmol/l (CGP 39551), respectively. The compounds dose-dependently blocked vestibular stimulation-induced convulsions in EL mice, 2 h after oral administration, with ED50 (95% CI) values of 135 (78-236) mumol/kg (CGP 37849) and 65 (45-94) mumol/kg (CGP 39551). In male Swiss albino mice, performance in the step-through passive avoidance procedure was dose-dependently impaired with ED50 (95% CI) values of 85 (56-157) mumol/kg (CGP 37849) and 27 (18-42) mumol/kg (CGP 39551). In addition performance of these animals in the rotarod test of motor coordination was impaired, 2 h after oral administration of CGP 39551, with an ED50 (95% CI) of 142 (100-201) mumol/kg. These findings demonstrate anticonvulsant activity in these potent NMDA antagonists after oral administration with CGP 39551 possessing greater relative potency. However, the unfavourable ratio of therapeutic dose versus dose inducing memory or motor impairment supports the prevailing notion that such adverse effects of the presently available compounds preclude the use of NMDA antagonists as long-term therapies.

2-Amino-5-phosphonovalerate↗
PubMed1988

Effect of single or chronic injection with a carbamate, propoxur, on the brain cholinergic system and behavior of mice.

Propoxur, an anticholinesterase carbamate, was injected singly (10 mg/kg, s.c.) or chronically (5 mg/kg/day, s.c., for 10 days) into mice. Animals were examined for effects on the cholinergic system in brain tissue and on behavior. Single injection caused an increase in brain acetylcholine (ACh) content at 10 and 60 min; and it caused decreases in acetylcholinesterase (AChE) activity at 10, 60 and 180 min, high-affinity choline uptake into synaptosomes at 10 and 60 min, and [3H]quinuclidinyl benzilate (QNB) binding at 10 min without causing any change in choline acetyltransferase (ChAT) activity. Open-field behavior and rotarod performance were depressed at 10 min and rectal temperature was decreased at 10, 60 and 120 min after a single injection. Chronic treatment caused decreases in high-affinity choline uptake and [3H]QNB binding 24 hr after the final injection without any changes in ACh content, AChE activity or ChAT activity. In behavioral tests conducted 10 min prior to daily administration, rotarod performance was slightly suppressed only during the period of injection. Although propoxur is considered to have effects similar to those of organophosphorus compounds, the changes observed in the present experiments seemed to be reversible.

Animals↗
PubMed2004

The effect of repeated isoflurane anesthesia on spatial and psychomotor performance in young and aged mice.

UNLABELLED: Exposure to general anesthesia may contribute to postoperative cognitive impairment in elderly patients, but the relationship remains poorly understood. We investigated whether aged mice, 18-19 mo, are more susceptible to postanesthetic cognitive impairment than young mice, 3-4 mo, using spatial memory (Barnes maze) and psychomotor (rotarod) tasks. Initially we studied the effect of a single anesthetic episode on asymptotic maze performance. We then tested whether repeated anesthesia would impair spatial memory and psychomotor performance to a greater extent in aged mice. Mice were anesthetized with isoflurane (1.4% atm) for 30 min; controls received 90% oxygen. Anesthesia, administered during the asymptotic period of maze learning, did not impair performance tested the following day (P > 0.05). Repeated anesthesia, 2-3 h after each session, did not impair overall maze or rotarod performance in young or aged mice (P > 0.05). Spatial learning appeared to be facilitated by anesthesia, F(1,204) = 7.97, P < 0.01 for pooled results. Asymptotic performance-when learning had stabilized-remained unimpaired in both the maze and rotarod tasks. These results suggest that an age-related risk of anesthetic-induced impairment appears to be limited to acquisition of a novel motor skill and that anesthesia alone does not lead to prolonged cognitive impairments in aged mice. IMPLICATIONS: This study demonstrates that repeated isoflurane general anesthesia impaired psychomotor performance in aged mice during the initial learning period; however, spatial learning improved and, overall, spatial memory and psychomotor performance were unimpaired. Thus, general anesthesia alone does not appear to result in prolonged cognitive deficits in aged mice.

Aging↗
PubMed2001

Role of 5-HT6 receptors in memory formation.

Mice lacking the 5-HT(6) receptor presented neither gross anatomical or behavioral abnormalities nor obvious changes in microscopic brain morphology, and their performance in rotarod, open field and novel object testing paradigms revealed no differences compared with wild-type animals. Nevertheless, an association between the 5-HT(6) receptor polymorphism C267T and Alzheimer's disease has been reported. Interestingly, the 5-HT(6) antisense oligonucleotide decreased 5-HT(6) gene expression and enhanced spatial learning acquisition in the water maze. Similarly, injection of the 5-HT(6) receptor antagonist Ro-04-6790 improved learning consolidation in an autoshaping task, while mCPP, scopolamine and dizocilpine decreased performance. The effect induced by scopolamine or dizocilpine, but not that induced by mCPP, was completely or partially reversed by Ro-04-6790. Ro-04-6790 did not modify the 8-OH-DPAT facilitatory effects on learning consolidation. Since Ro-04-6790 facilitatory effect was unaffected by 5-HT(1A), 5-HT(2A/2B/2C), 5-HT(3), 5-HT(4) or 5-HT(7) receptor blockade, the facilitatory effect induced by Ro-04-6790 involved specifically 5-HT6 receptors. Similarly, the 5-HT(6) receptor antagonist SB-271046 improved retention in the water maze and produced a significant performance improvement in aged rats in an operant-delayed alternation task. A series of Ro-04-6790 analogues that penetrate the brain and specifically bind to 5-HT(6) receptors reversed scopolamine-induced retention deficit in a passive avoidance learning test. Collectively, these data provide further support to the notion that 5-HT systems, via 5-HT(6) receptors, also play a significant role in memory formation under normal and dysfunctional memory conditions.

Journal Article↗
PubMed1982

Assessment of the effects of acrylamide, methylmercury, and 2,5-hexanedione on motor functions in mice.

Neurotoxic effects of acrylamide, methylmercury, and 2,5-hexanedione were studied in forth female BALB/c mice. The chemicals were dissolved in distilled water and administered via light-tight drinking bottles. Three control groups were used. The first received distilled water, the second received concentrated saccharin solution to assess the effects of reduced water intake, and the third was maintained on a reduced food diet. Motor functions were quantified by measuring landing foot-spread and rotarod performance. Baseline data were collected before dosing started. Mice were placed, twice weekly, on an accelerating rotarod, and their retention time was recorded. In the landing foot-spread test, the experimenter dropped mice from 15 cm onto a flat, smooth surface once a week. The hindlimb splay was then measured by the examiner. Both experimenter and examiner were unaware of the identity of each group (except of the food deprived group, in the case of the experimenter) during the first exposure. Decreased retention time and increased hindlimb splay were observed in mice after 12 d of exposure to acrylamide. Recovery followed treatment cessation. Increased hindlimb splay preceded an obvious decline of rotarod performance in the group receiving the 10 ppm of methylmercury solution. Mice receiving the 20 and 40 ppm of methylmercury solutions did not display any change in these tests before overt signs of toxicity. 2,6-Hexanedione produced a small decline in performance to a constant level after 85 d of exposure. After dosing termination, performance returned to baseline values. Control groups showed no change in performance on either the rotarod or the landing foot-spread test. Our data show that the rotarod and hindlimb splay tests in mice are about equal in sensitivity to the effects of the neurotoxic chemicals tested.

Acrylamides↗