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At least 631 records · Page 35Linked to original sources
PubMed2005

Rats with scopolamine- or MK-801-induced spatial discrimination deficits in the cone field task: animal models for impaired spatial orientation performance.

Spatial cognition appears to be compromised in elderly and in patients suffering from dementia. These deficits are believed to be modelled, at least partly, by the administration of scopolamine or MK-801 in normal adult animals. In order to establish an animal model suited for the evaluation of putative cognition enhancers, we assessed the effects of scopolamine (0.3, 0.5, 0.7 mg kg(-1), i.p.) and MK-801 (0.07, 0.08, 0.09 mg kg(-1), s.c.) in rats trained in the cone field. This task allows the simultaneous investigation of working memory (WM), reference memory (RM) and search strategies. Scopolamine and MK-801 reliably induced spatial cognition deficits in the cone field without inducing behavioural side effects. This task appears to be suited for assessing the effects of putative cognition-enhancing compounds on spatial cognition.

Animals↗
PubMed2006

Enhancing effects of nicotine and impairing effects of scopolamine on distinct aspects of performance in computerized attention and working memory tasks in marmoset monkeys.

With the CAmbridge Neuropsychological Test Automated Battery (CANTAB), computerized neuropsychological tasks can be presented on a touch-sensitive computer screen, and this system has been used to assess cognitive processes in neuropsychiatric patients, healthy volunteers, and species of non-human primate, primarily the rhesus macaque and common marmoset. Recently, we reported that the common marmoset, a small-bodied primate, can be trained to a high and stable level of performance on the CANTAB five-choice serial reaction time (5-CSRT) task of attention, and a novel task of working memory, the concurrent delayed match-to-position (CDMP) task. Here, in order to increase understanding of the specific cognitive demands of these tasks and the importance of acetylcholine to their performance, the effects of systemic delivery of the muscarinic receptor antagonist scopolamine and the nicotinic receptor agonist nicotine were studied. In the 5-CSRT task, nicotine enhanced performance in terms of increased sustained attention, whilst scopolamine led to increased omissions despite a high level of orientation to the correct stimulus location. In the CDMP task, scopolamine impaired performance at two stages of the task that differ moderately in terms of memory retention load but both of which are likely to require working memory, including interference-coping, abilities. Nicotine tended to enhance performance at the long-delay stage specifically but only against a background of relatively low baseline performance. These data are consistent with a dissociation of the roles of muscarinic and nicotinic cholinergic receptors in the regulation of both sustained attention and working memory in primates.

Acetylcholine↗
PubMed2004

Antagonism of anticholinesterase (DFP) toxicity by donepezil plus scopolamine: a preliminary study.

Studies in animals exploring the antagonism of the cholinesterase inhibitors soman and sarin have shown that pretreatment with low doses of the centrally acting cholinesterase inhibitor, physostigmine, alone or in conjunction with the centrally acting anticholinergic agent, scopolamine, is effective against their lethality and toxicity. The current study evaluated the effects of pretreatment with the oral anticholinesterase agent, donepezil (Aricept, 2.0 mg/kg), used to treat Alzheimer's disease, with and without scopolamine in decreasing the hypothermic, hypokinetic, and diarrhea-inducing effects of the irreversible long-acting cholinesterase inhibitor diisopropyl fluorophosphate (DFP, 1.0 mg/kg) in adult Flinders sensitive line (FSL) male rats. Donepezil alone and donepezil plus scopolamine (0.1 mg/kg) to a greater extent antagonized the decrease in temperature, hypoactivity, and induction of diarrhea due to DFP observed at 4 h after its administration. However, donepezil alone induced hypothermia at 1 and 2 h after treatment. Therefore, these preliminary findings are encouraging, but many additional studies are needed to establish the effectiveness of donepezil as a prophylactic agent against irreversible cholinesterase inhibition by DFP.

Animals↗
PubMed2004

Effects of MDMA administration on scopolamine-induced disruptions of learning and performance in rats.

Functional deficits following short-course high-dose administration of 3,4-methylenedioxymethamphetamine (MDMA) have been difficult to characterize despite evidence indicating that MDMA is neurotoxic in several species. Therefore, the present research used rats trained to respond under a complex behavioral procedure (i.e., a multiple schedule of repeated acquisition and performance of response chains), pharmacological challenge with scopolamine and neurotransmitter assays to examine the effects of MDMA neurotoxicity on learning. Prior to MDMA administration, 0.032-0.32 mg/kg of scopolamine produced dose-dependent rate-decreasing and error-increasing effects in both components of the multiple schedule. Administration of 10 mg/kg of MDMA twice per day for 4 days also produced rate-decreasing and error-increasing effects on these days, but responding returned to baseline levels several days after the final injection. In contrast to the recovery of responding, this regimen of MDMA in untrained rats significantly reduced levels of both serotonin and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA), for 13-14 days. Furthermore, the rate-decreasing and error-increasing effects of scopolamine were significantly attenuated after MDMA treatment. These results indicate that certain complex operant behaviors rapidly recover from the effects of short-course high-dose MDMA administration, despite the reduced levels of serotonin in the central nervous system (CNS), and that this MDMA-induced loss of serotonin may affect cholinergic transmission.

Animals↗
PubMed2006

Beneficial effects of galantamine on performance in the object recognition task in Swiss mice: deficits induced by scopolamine and by prolonging the retention interval.

Episodic memory has been found to be impaired in several neuropsychiatric disorders. The object recognition task (ORT), introduced by Ennaceur and Delacour [Ennaceur A., Delacour J. A new one-trial test for neurobiological studies of memory in rats: 1. Behavioral data. Behav Brain Res 1988; 31: 47-59.], is a method to measure a specific form of episodic memory in rats and mice. It is based on the spontaneous behavior of rodents and can be considered as a retention test completely free of reference memory components. Therefore, the ORT has been increasingly used as an experimental tool in assessing drug effects on memory and investigating the neural mechanisms underlying learning and memory. In the present study, the main goal was to evaluate the effects of galantamine in Swiss mice in the ORT on scopolamine-induced deficits and with different retention intervals. Mice had a good object recognition memory at the 15 min retention intertrial interval (ITI). Object discrimination was absent at the longer intervals (1 h, 4 h and 24 h). Galantamine (10 mg/kg, administered s.c., 30 min prior to acquisition) partially reversed effects of scopolamine (0.63 mg/kg, administered s.c., 30 min prior to acquisition) and normalized performance to control levels. A lower dose of galantamine (0.63 mg/kg) was also investigated when two different retention intervals (15 min and 1 h) were used. Galantamine (0.63 mg/kg) had no adverse effects. Solvent-treated mice in the 1 h ITI condition did not discriminate between the novel and the familiar object (discrimination index was equal to zero), while galantamine (0.63 mg/kg)-treated mice attained a good object recognition memory performance. In conclusion, galantamine was shown to possess memory-enhancing effects in two conditions that reduced object discrimination: scopolamine-induced deficits and when a longer retention interval was used.

Animals↗
PubMed1997

The GABA(B) receptor antagonist CGP36742 attenuates the baclofen- and scopolamine-induced deficit in Morris water maze task in rats.

Effects of CGP36742 (3-aminopropyl-n-butylphosphinic acid), an orally active GABA(B) receptor antagonist, on the baclofen- and scopolamine-induced deficit of place learning in the Morris water maze task were examined in rats. Rats were given four training trials per day with the submerged platform at a fixed location in the maze for 4 days. On day 4, the rats were required to swim in the pool without the platform after the fourth training trial (probe test). Intraperitoneal injection of baclofen (4 mg/kg) or scopolamine (0.3 mg/kg) significantly increased the escape latency to reach the platform and decreased the duration in the quadrant where the platform had been originally located. Increased latency in the training trials and decreased duration in the probe test induced by baclofen or scopolamine were significantly attenuated by oral administration of CGP36742 at doses of 10 and 30 mg/kg. In the rotarod test, CGP36742 at a dose of 100 mg/kg but not at doses of 10 or 30 mg/kg antagonized the baclofen-induced motor incoordination. Thus, there was dissociation between the effective doses of CGP36742 in the learning task and those in the sensory motor test. These results suggest the possible involvement of cholinergic systems as well as GABA(B) receptor systems in the CGP36742 action.

Animals↗
PubMed1997

WAY 100635, a 5-HT1A receptor antagonist, prevents the impairment of spatial learning caused by intrahippocampal administration of scopolamine or 7-chloro-kynurenic acid.

The effect of WAY 100635, a 5-HT1A receptor antagonist, on the impairment of spatial learning caused by intrahippocampal administration of scopolamine, a cholinergic muscarinic receptor antagonist, or 7-chloro-kynurenic acid, an antagonist at the glycine site associated with the NMDA receptor complex, was studied in a two-platform spatial discrimination task. Scopolamine (4 microg/microl) or 7-chloro-kynurenic acid (3 microg/microl), administered bilaterally into the CA1 region of the dorsal hippocampus 10 min before each training session, impaired choice accuracy with no effect on choice latency and errors of omission. Administered subcutaneously at 1 (but not at 0.3) mg/kg 30 min before each training session, WAY 100635 did not modify the acquisition of spatial learning, but prevented the impairment of choice accuracy caused by intrahippocampal scopolamine or 7-chloro-kynurenic acid. These findings suggest that blockade of 5-HT1A receptors can compensate the loss of cholinergic or NMDA-mediated excitatory input to pyramidal cells in the hippocampus. The mechanisms involved and the importance of these findings for the symptomatic treatment of memory disorders in man are discussed.

Animals↗
PubMed1999

FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a novel potential antidementia drug, restores the regional cerebral blood flow response abolished by scopolamine but not by HA-966: a positron emission tomography study with unanesthetized rhesus monkeys.

The interactions of FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a novel potential antidementia drug, with cholinergic and glutamatergic neuronal systems were evaluated with respect to its effects on the regional cerebral blood flow (rCBF) response to vibrotactile stimulation in unanesthetized rhesus monkeys with [15O]H2O and high resolution positron emission tomography (PET). Under a saline condition, the vibrotactile stimulation given on the right forepaw induced a significant increase in the rCBF response in the contralateral somatosensory cortex of the monkey brain. Systemic administration of scopolamine (50 microg/kg, i.v.), a muscarinic cholinergic receptor antagonist, completely abolished the rCBF response to the stimulation, and the abolishment lasted, at least, up to 4 h after scopolamine injection. The scopolamine-induced abolishment of rCBF response was restored by the administration of FK960 at relatively wide dosing range from 1 to 1000 microg/kg (i.v. ), and the recovery by FK960 on the rCBF response lasted for 1 h following the administration of FK960 at doses of 100 and 1000 microg/kg. On the other hand, the rCBF response abolished by 1000 microg/kg of (+)-3-amino-1-hydroxy-2-pyrrolidone (HA-966), an antagonist of the glycine modulatory site on the N-methyl-d-aspartate (NMDA) receptors, was not restored by FK960 (1000 microg/kg, i.v.). These findings suggest that FK960 reverses the abolished rCBF response to somatosensory stimulation via enhancement of cholinergic neurotransmission but not via the glutamatergic one.

Animals↗
PubMed2000

Improvement by low doses of nociceptin on scopolamine-induced impairment of learning and/or memory.

The effects of fmol doses of nociceptin/orphanin FQ on scopolamine-induced impairment of learning and/or memory were examined using spontaneous alternation of Y-maze and step-down type passive avoidance tasks. While fmol doses of nociceptin alone had no effect on spontaneous alternation or passive avoidance behavior in normal mice, administration of nociceptin (10 and/or 100 fmol/mouse) 30 min before spontaneous alternation performance or the training session of the passive avoidance task, significantly improved the scopolamine-induced impairment of spontaneous alternation and passive avoidance behavior. This ameliorating effect was not antagonized by nocistatin (0.5 and 5.0 nmol/mouse, i.c.v.), naloxone benzoylhydrazone (2.3, 11.2, and 56.1 micromol/kg, s.c.) or nor-binaltorphimine (4.9 nmol/mouse, i.c.v.). These results indicated that very low doses of nociceptin ameliorate impairments of spontaneous alternation and passive avoidance induced by scopolamine, and suggested that this peptide has bidirectional modulatory effects on learning and memory; impairment at high doses and amelioration at low doses.

Analgesics, Opioid↗
PubMed2000

The effects of some K(+) channel blockers on scopolamine- or electroconvulsive shock-induced amnesia in mice.

The effects of three K(+) channel blockers, 4-aminopyridine, 3, 4-diaminopyridine and apamin, on scopolamine- or electroconvulsive shock-induced amnesia were investigated in mice by using a one-trial step-down passive avoidance system. Scopolamine and electroconvulsive shock reduced the retention latency of passive avoidance, which indicated the amnestic effect of these treatments. 4-Aminopyridine, 3,4-diaminopyridine and apamin injected immediately after the acquisition trial, reversed the amnestic effect of scopolamine or electroconvulsive shock in a dose-dependent manner. None of the drugs or electroconvulsive shock treatment affected the rotarod or activity cage performance of the mice. These results indicate that K(+) channel blockers may improve cognitive deficits when memory is impaired by a drug or any other manipulation.

4-Aminopyridine↗
PubMed1998

Reversal of scopolamine-induced deficits in radial maze performance by (-)-huperzine A: comparison with E2020 and tacrine.

The effects of (-)-huperzine A ((5R,9R,11E)-5-amino-11-ethylidene-5,6,9,10-tetrahydro-7-methyl-5, 9-methanocycloocta[b]pyridin-2(1H)-one), and of the hydrochloride salt of E2020 ((R,S)-1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]-methyl piperidine) and tacrine (9-amino-1,2,3,4-tetrahydroacridine), on the scopolamine-induced memory deficits in rats were compared in a radial maze, using a 4-out-of-8 baiting procedure. Scopolamine (0.15 mg/kg, i.p.) caused significant impairment in the rats' ability to fulfil the radial maze task. (-)-Huperzine A (0.2-0.4 mg/kg, p.o.; 0.1-0.4 mg/kg, i.p.) had greater efficacy than E2020 (0.6-0.9 mg/kg, p.o.; 0.3-0.6 mg/kg, i.p.) and tacrine (1.5-2.5 mg/kg, p.o.; 0.3-0.6 mg/kg, i.p.) on the improvement of scopolamine-induced working and reference memory errors, respectively. There appeared to be an inverse bell-shape dose-dependent effect for all three compounds tested. The compared data demonstrate that (-)-huperzine A is the most potent and orally active acetylcholinesterase inhibitor of the three, and fits more closely the established criterions for an ideal acetylcholinesterase inhibitor to be used in clinical studies.

Alkaloids↗
PubMed1999

Effect of rivastigmine on scopolamine-induced memory impairment in rats.

The effect of rivastigmine on memory impairments induced in rats by scopolamine (0.5 mg/kg) was assessed in the Morris water maze and passive avoidance tests and compared with that of tacrine (2.5-17.7 mg/kg). Rivastigmine, (0.5-2.5 mg/kg) inhibited cholinesterase in the cortex and hippocampus by 21-60% and antagonised the deficits in working and reference memory. Tacrine (12.5 and 17.7 mg/kg) produced significantly less inhibition of cholinesterase in the hippocampus but more in the striatum than rivastigmine (0.75 and 1.5 mg/kg) and only antagonised the deficit in reference memory. Rivastigmine (1.5 and 2.5 mg/kg) or tacrine (12.5 mg/kg), injected immediately after completion of the acquisition trial in the passive avoidance test, antagonised the deficit induced by scopolamine (1 mg/kg) in memory retention. The inability of higher doses of the cholinesterase inhibitors to antagonise memory deficits induced by scopolamine may be related to excessive cholinergic stimulation in the central nervous system.

Animals↗
PubMed1999

Bovine brain phosphatidylserine attenuates scopolamine-induced amnesia.

The effects of bovine cerebral cortex phosphatidylserine (BCPS) on the memory impairment induced by scopolamine in mice tested in the plus-maze discriminative avoidance task were investigated. Swiss male mice received daily i.p. 50 mg/kg BCPS or 0.2 M Tris pH 7.4 (TRIS) for 5 days. Twenty-four hours after the last injection, the animals received 1 mg/kg scopolamine (BCPS-SCO and TRIS-SCO) or saline (BCPS-SAL and TRIS-SAL) i.p. After 20 min, the animals were submitted to discriminative avoidance conditioning. In the test, performed 24 h later, BCPS-SCO, BCPS-SAL, and TRIS-SAL (but not TRIS-SCO) mice spent significantly less time in the aversive enclosed arm of the discriminative avoidance apparatus when compared to the time spent in the nonaversive enclosed arm. The results suggest that BCPS attenuates scopolamine-induced amnesia in a discriminative avoidance task.

Amnesia↗
PubMed2000

Simultaneous determination of scopolamine, hyoscyamine and littorine in plants and different hairy root clones of Hyoscyamus muticus by micellar electrokinetic chromatography.

Hyoscyamus muticus hairy root clones were established following infection with Agrobacterium rhizogenes strains A4, LBA-9402 and 15834 and with A. tumefaciens strain C58C1pRTGus104. The accumulation of tropane alkaloids hyoscyamine, littorine and scopolamine was evaluated by micellar electrokinetic capillary electrophoresis. Littorine was reported for the first time in these clones as well as in the roots of the intact plant and confirmed by collision induced dissociation-mass spectrometry. Tropane alkaloid content in hairy roots was compared with leaves and roots of normal plants at two vegetative stages. Significant differences appeared between the alkaloid contents of the different clones. In particular, all the hairy root clones and the roots of the intact plant produced 1.5-3 and 4.5-9 times more littorine than scopolamine, respectively. The only exception was clone KB7, carrying the h6h gene, which overproduced scopolamine. The aerial parts of H. muticus plants did not contain any littorine, thus indicating different transportation or translocation mechanisms of the various tropane alkaloids.

Atropine↗
PubMed1997

Reduction of dizocilpine and scopolamine-induced deficits in avoidance responding by SCH 54388, a metabolite of felbamate.

Felbamate (2-phenyl-1,3-propanediol dicarbamate) is a novel antiepileptic agent with a unique structure and mechanism of action, possibly involving binding sites at the N-methyl-D-aspartate receptor (NMDA) complex. A monocarbomate metabolite of felbamate (SCH 54388) was compared to felbamate using a mouse passive-avoidance paradigm (PAR). SCH 54388 was markedly free of toxic side effects up to doses of 300 mg/kg, sc. SCH 54388 reduced the deficit-producing effects of either scopolamine, a cholinergic antagonist, or dizocilpine (MK-801), an NMDA receptor channel blocker, in a dose-dependent manner. The effective dose range of SCH 54388 was between 0.01 and 10 mg/kg, sc. SCH 54388 was also orally active at doses between 0.1 and 10 mg/kg. Felbamate also reduced scopolamine and dizocilpine antagonism, but was less potent than SCH 54388, reducing scopolamine-induced deficits at 1 to 3 mg/kg, sc. in a dose-dependent manner and reducing deficits induced by dizocilpine at doses of 0.1 and 3 mg/kg, SC. The reduction of dizocilpine-induced deficits by felbamate was not dose dependent. These results suggest that SCH 54388 has a mechanism of action involving either directly or indirectly, glutaminergic and cholinergic central neuronal systems.

Animals↗
PubMed1998

Neonatal scopolamine or antidepressant treatment: effect on development of hamster circadian rhythms.

Chronic treatment of young rodents with drugs altering monoamine metabolism has been reported to produce lasting effects on behavior that resemble human affective disorders. To test the generality of this finding, scopolamine, imipramine, or clomipramine was injected daily between the ages of 8 and 21 days in golden hamsters. Wheel-running rhythms were monitored continuously from the age of 4 to 20 weeks of age to test the hypothesis that neonatal treatments would lower the amplitude of biological activity rhythms in adults. Of these three neonatal treatments only scopolamine altered running rhythms, significantly increasing the amplitude of running rhythms in adult hamsters under both entrained and free-running conditions. Hamsters treated neonatally with scopolamine were also more sensitive to the hypothermic effects of the muscarinic agonist, oxotremorine, as adults. These data indicate that neonatal exposure to cholinergic receptor blockade may produce long-lasting changes in biological rhythm characteristics related to upregulation of muscarinic receptors.

Aging↗
PubMed2002

Water maze versus radial maze: differential performance of rats in a spatial delayed match-to-position task and response to scopolamine.

Studies rarely assess treatment effects across tasks; the present experiments addressed this issue. In Experiments 1 and 2, rats (n=12) were trained and then tested with variable delays on a spatial match-to-position task sequentially in the water and radial mazes (in counterbalanced order). Experiment 1 compared the effect of 0-, 60- and 1440-min delays on performance in both mazes. Rats required fewer (P<0.05) mean (+/-S.E.M.) sessions to reach criterion performance in the water (11.0+/-1.0) versus radial maze (19.3+/-2.2). In test sessions, performance was impaired delay-dependently when scores were averaged across the two tasks (P<0.05) but no significant effect of task or task x delay interaction was found. In the second experiment, the same rats were retrained and tested with 0-, 1-, 3- and 5-min delays in both mazes and testing followed the administration of scopolamine (0, 0.1, 0.4 and 0.8 mg/kg). The mean (+/-S.E.M.) number of acquisition sessions was similar in the radial (6.33+/-0.34) and water maze (6.08+/-0.46). On the sample portion of trials, performance was impaired at the 0.8 mg/kg dose of scopolamine (P<0.02) in the radial maze only. On the recognition portion of trials in the radial maze, the 0.4 and 0.8 mg/kg doses of scopolamine impaired performance whereas in the water maze task the 0.8 mg/kg dose impaired performance. The pattern of results may reflect different natural tendencies of rats to alternate (win-shift) versus not alternate (win-stay) in dry land versus swim tasks.

Animals↗
PubMed2002

Effects of scopolamine and D-cycloserine on non-spatial reference memory in rats.

The aim of the present work was to use a three-choice simultaneous brightness discrimination test to examine the retention of non-spatial reference memory in rats treated with scopolamine (0.5 mg/kg) alone and in combination with various concentrations of D-cycloserine (DCS) (5, 15 and 50 mg/kg). Scopolamine given 1 h before testing for retention was found to increase both the number of errors and the number of trials necessary to reach criterion. The three doses of DCS reduced this increase significantly and resulted in a U-shaped dose-response curve, where 15 mg/kg had a stronger compensatory effect than both 5 and 50 mg/kg. Control experiments were performed to confirm that the observed response was not due to non-mnemonic factors. Our results indicate that scopolamine and DCS affect non-spatial reference memory in a similar manner as shown for spatial reference memory.

Animals↗