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PubMed2002

Elevated T-maze as an animal model of memory: effects of scopolamine.

The elevated T-maze (ETM) is a putative model for the assessment of anxiety and memory in rodents. This study was designed to further evaluate the utility of the ETM in the study of memory processes. We compared the performance of rats in the ETM, the water maze (WM) and the two-way avoidance task (TWA), after pretreatment with scopolamine (SCO; 0.3 or 1.2 mg/kg i.p.). In the ETM, rats were first trained to meet the criterion of remaining inside the enclosed arm for 300 seconds. Seventy-two hours after training, a retrieval test session was performed. At the lower dose, SCO impaired performance in the retrieval session on all three tasks, whereas in the training session an effect was noted only on the WM task. At the higher dose, SCO impaired the performance of rats in the training sessions for ETM and WM, but not TWA. In a fourth experiment using the elevated plus-maze, SCO showed anxiolytic-like effects at the higher dose only. In conclusion, the effects of SCO in rats submitted to the ETM were dose dependent, with the lower dose exerting a selective effect detected only on retrieval, whereas the higher dose induced motor effects that disrupted inhibitory avoidance acquisition, resulting in impaired retrieval. The results are discussed in terms of the utility of the ETM in the study of drug effects and the neurobiological mechanisms underlying anxiety, learning and memory.

Animals↗
PubMed2004

Scopolamine given pre-Trial 1 prevents the one-trial tolerance phenomenon in the elevated plus-maze Trial 2.

A learned avoidance response has been one of the hypotheses proposed to explain the 'one-trial tolerance' (OTT) phenomenon, which represents a drug's loss of anxiolytic-like effect in the elevated plus-maze (EPM) test in experienced rodents. Based on these facts, if some kind of learning occurs throughout Trial 1, then an impairment of its acquisition would maintain the drug's anxiolytic-like effect on Trial 2. Using male Wistar rats, the present study examined whether scopolamine (SCO; 0.5-1.5 mg/kg), a drug that impairs learning acquisition, given 30 min prior to Trial 1, actually prevents the OTT phenomenon to either the midazolam (MDZ; 0.5 mg/kg) or the memantine (MEM; 8.0 mg/kg) anxiolytic-like effect on the EPM Trial 2 (48 h later). According to the results, both MDZ and MEM increased open-arm exploration (indicating anxiolysis) on Trial 2 only in rats that had been treated previously with 1.5 mg/kg SCO. These results were observed in the absence of change in general exploratory activity. The present findings suggest that SCO impaired the acquisition of the behavioral strategy to cope with the subsequent EPM exposure that supposedly underlies the OTT phenomenon, thereby revealing the anxiolytic-like effects of MDZ and MEM on Trial 2.

Adaptation, Psychological↗
PubMed2006

Effects of biasing the location of stimulus presentation, and the muscarinic cholinergic receptor antagonist scopolamine, on performance of a 5-choice serial reaction time attention task in rats.

A major purpose of the present studies was to determine the effects of varying the relative frequency, or bias, of stimulus presentation at different locations in a five-choice serial reaction time attention task. Training sessions were conducted in which the stimulus duration was held constant at 2 s and, initially, stimuli were presented with equal probability above each of the levers. During testing sessions, however, stimulus duration was either 0.2 or 2 s, and the frequency of presentation was varied among no bias, a middle bias, a left bias or a right bias condition. The training conditions were then changed such that the frequency of presentation was always a left bias, and test sessions were again conducted with no, middle, left or right bias. In the presence of the 0.2-s, but not the 2.0-s, stimulus, the percentage of correct responding on each of the choice levers during test sessions varied directly with the bias conditions in that the percentage of correct responding was highest at the most frequently presented location and lowest at the least frequently presented location. In addition, scopolamine, but not metscopolamine, increased omissions while also increasing anticipatory responses in rats trained under left-bias conditions and tested under right-bias conditions. The present findings suggest that varying the frequency of stimulus location can provide additional measures of attention in the five-choice serial reaction time task.

Animals↗
PubMed1980

Failure of intramuscularly administered lorazepam and scopolamine-morphine premedication to produce amnesic effects to supplement conduction anaesthesia.

Patients undergoing surgery under regional anaesthesia often prefer to be sedated and do not later want to recall the procedure. One hundred and twenty-one patients scheduled for various surgical procedures under epidural, spinal, sacral, or brachial plexus blockades received 1 mg/kg of pethidine, 0.007 mg/kg of scopolamine, plus 0.14 mg/kg of morphine, or 0.03 mg/kg or 0.06 mg/kg or lorazepam intramuscularly as preanaesthetic medication before the operation. The patients's self-assessments of degree of fatigue and apprehension were similar after each premedication when assessed before operation. Postoperative anxiety and confusion as well as need for postoperative care and supervision were greatest after 0.06mg/kg of lorazepam. Significantly (P smaller than 0.05 to P smaller than 0.01) fewer patients given 0.06 mg/kg or lorazepam remembered different events and procedures carried out on them before and after operation than those given other premedications, but no significant differences were noted in patients' ability to recall the performance of operation when asked on the following day. Seventy-seven, 63, and 57% of patients receiving 0.06 mg/kg of lorazepam remembered the start of blockade, performance of operation, and stay in recovery room, respectively. Intravenous sedation should be preferred to these intramuscularly administered premedications if drug-induced amnesia is sought to supplement local anaesthetic techniques.

Adult↗
PubMed1987

Premedication with midazolam in out-patient general anaesthesia. A comparison with morphine-scopolamine and placebo.

Strong premedication may prolong recovery and cause side-effects after short surgical procedures in general anaesthesia. To be operated without premedication may be unpleasant for the patient. Midazolam is a water-soluble benzodiazepine with rapid onset and short half-life. In a randomized study with 193 female patients, we compared the effects and side-effects of three different premedicants i.m.: midazolam, morphine-scopolamine (Mo-Scop) and placebo. Midazolam and Mo-Scop had an equal and significantly better effect than placebo on preoperative anxiety and alertness. Side-effects like nausea, dry mouth and prolonged recovery occurred significantly more often in the Mo-Scop than the midazolam or placebo groups. The midazolam-premedicated patients had significantly more amnesia compared with the other two groups. Only 3% of the patients would prefer no medication before anaesthesia, whereas 80% would prefer a combination of an anxiolytic and hypnotic premedication. Sixty-three percent of the patients would prefer a premedicant administered by injection. The results indicate that midazolam i.m. is an effective premedicant, with few side-effects, for short procedures in general anaesthesia.

Adult↗
PubMed1988

Pharmacokinetic implications for the clinical use of atropine, scopolamine and glycopyrrolate.

Several specific and sensitive new methods for determining atropine and its metabolites in biological fluids have increased the possibility to characterise the pharmacokinetic properties of this antimuscarinic agent. Following i.v. injection, atropine disappears very quickly from the circulation, resembling its fast onset of action. Age, but not sex, appears to have a clear effect on its kinetics, explaining at least partly the higher sensitivity of very young and very old patients to this anticholinergic agent. Following i.m. or oral atropine administration, typical anticholinergic effects coincide quite well with the absorption rate of the drug, indicating that the premedication should be given about 1 and 2 h before induction of anaesthesia. A sufficient absorption after rectal administration offers an alternative treatment, especially in children. Differing from its placental transfer, atropine has a delayed and incomplete lumbar cerebrospinal fluid penetration, indicating a fundamental difference between these two biological membranes. Oropharyngeally administered atropine has a very variable absorption, but inhaled or intratracheally given drug has produced interesting new results, e.g. pulmonary atropine administration appears to have clinical significance in special situations, such as cardiac arrest and organophosphate poisoning (military personnel). Depending on the method used, different data on the metabolism and excretion for atropine have been reported and therefore further studies are needed in this respect. The pharmacokinetics of scopolamine and glycopyrrolate and their relation to clinical response are poorly understood.

Aging↗
PubMed1989

Effect of a slow release transcutaneous scopolamine application on salivary flow, pH, buffering action, and salivary levels of Streptococcus mutans and lactobacilli.

A motion sickness plaster releasing a powerful antisialogogic agent, scopolamine, was tested in a double blind clinical trial for its effect on salivary parameters in 14 healthy young men. The agent caused a decline in salivary flow rates, which was most pronounced during unstimulated conditions. Salivary pH and buffer capacity were also reduced. Salivary levels of Streptococcus mutans and lactobacilli showed a tendency to increase during 2 days on the antisialogogic agent, but the effect on S. mutans levels was not statistically significant.

Administration, Cutaneous↗
PubMed1986

Pharmacokinetics and clinical effects of scopolamine in caesarean section patients.

A new method (ELISA) was used to evaluate the pharmacokinetics of scopolamine following intravenous (0.005 mg/kg), intramuscular (0.01 mg/kg), and oropharyngeal (0.035 mg/kg) administration of the drug to pregnant patients anaesthetized for caesarean section. After intravenous (N = 4) the drug fast disappeared from the circulation with a half-life of about 5 min., and the serum levels generally were measurable up to 3 hours, mean elimination half-life was 1.85 hours. A fast absorption was found after intramuscular injection, tmax = 10 min. (N = 4), and the drug had a clinically significant oropharyngeal absorption as well, tmax was around 1 hour (N = 6). The intramuscular and oropharyngeal, but not the intravenous, administrations produced a marked postoperative sedative and amnesic effects. All three administration ways caused a significant antisecretory action.

Administration, Oral↗
PubMed2003

The ameliorating effects of cognition-enhancing Chinese herbs on scopolamine- and MK-801-induced amnesia in rats.

The study was to investigate the ameliorating effects of three Chinese herbs--Achyranthes bidentata (AB), Ophiopogon japonicus (OJ) and Cnidium monnieri (CM) on scopolamine (SCOP)- and MK-801-induced amnesia by using a passive avoidance task in rats. AB, OJ and CM at 0.1 and 0.3 g/kg prolonged the step-through latency (STL) of the retention trial. In addition, AB, OJ and CM reversed the STL shortened by MK-801, but only AB reversed the STL shortened by SCOP. In conclusion, these Chinese herbs possess cognition-enhancing activities and anti-amnestic effects, but the mechanism of the effect of AB was different from those of OJ and CM.

Achyranthes↗
PubMed1996

Behavioral responses induced by repeated treatment with methamphetamine alone and in combination with scopolamine in rats.

Repeated amphetamine (A) or methamphetamine (M) treatment induces behavioral sensitization and drug conditioning. The present study compared behavioral sensitization and drug conditioning between treatments with M combined with scopolamine (S) and M alone with respect to a reciprocal balance between the dopaminergic and inhibitory cholinergic systems in rats. Repeated treatment with M (4.0 mg/kg i.p.) combined with S (0.5 mg/kg i.p.) (MS) produced progressive enhancement of stereotyped behavior, compared with repeated M treatment alone. Repeated MS treatment induced focussed stereotyped behavior that was elicited by every challenge injection of not only MS and M, but also partially by S. MS- but not M-sensitized rats exhibited conditioned responses to a tone (300 Hz, 100 dB) associated with drug state, suggesting that MS-induced pronounced behavioral sensitization may lead to an enhanced conditioned response to the conditioned stimulus (CS) of a tone. It is suggested that MS-induced behavioral sensitization may be mediated via a reciprocal balance between the dopaminergic and cholinergic systems in favor of a dopaminergic dominance, and that such a balance may be involved in the conditioning to the drug-associated tone CS.

Animals↗
PubMed1985

Alteration of the rat exocrine pancreas after chronic scopolamine administration.

N-Methyl scopolamine (NMS) 25 mg kg-1 was given to rats for 14 days as a single daily intraperitoneal injection or by constant infusion through osmotic minipumps placed in the abdominal cavity. The anticholinergic drug reduced significantly body and pancreatic weights, and total pancreatic DNA contents, an indication of tissue growth inhibition. Total enzyme and protein contents were however significantly increased with the drug infusion more efficiently than by the daily injection. It is suggested that pancreatic hypertrophy observed after NMS treatment can be ascribed partially to inhibition of enzyme release elicited by blocking the enteropancreatic reflex causing over a long period enzyme accumulation in the gland. In conclusion, chronic anticholinergic treatment resulted in pancreatic aplasia and hypertrophy and could serve as a good model to study muscarinic receptor modulation in the pancreas.

Animals↗
PubMed2004

Presumed central anticholinergic syndrome from inadvertent intravenous hyoscine hydrobromide (scopolamine) injection.

We present a case of presumed central anticholinergic syndrome due to a drug administration error. A 35-year-old woman was slow to emerge from anaesthesia for laparoscopic biliary surgery. Postoperative neurological and metabolic abnormalities were later diagnosed as central anticholinergic syndrome. Only after resolution of the clinical problems did the drug error origin of the syndrome become apparent. It was realized that hyoscine hydrobromide (scopolamine) had been inadvertently administered intraoperatively for biliary relaxation, instead of hyoscine butylbromide. This case report describes central anticholinergic syndrome and highlights potential problems involved for anaesthetists administering drugs they do not commonly use.

Adult↗
PubMedDate not supplied

Relative potency of the atropine-like effects of a new parasympatholytic drug, scopolamine-N-(cyclopropyl methyl) bromide and those of hyoscine-N-butyl bromide.

A double-blind crossover trial with a 4-point bioassay was carried out in 8 convalescent in-patients to study the relative potency of scopolamine-N-(cyclopropyl methyl) bromide (DA 3177), a new parasympatholytic drug, administered at doses of 2.5 mg and 5 mg i.v., and hyoscine-N-butyl bromide, administered at doses of 10 mg and 20 mg i.v., in producing atropine-like effects. The results showed that the effects on heart rate and near point of accommodation were slightly less with DA 3177, while its effects on salivary secretion were a little greater than those of hyoscine-N-butyl bromide. It is suggested that study of the pharmacodynamic effects of parasympatholytic drugs is a relatively simple way of predicting which doses should be effective spasmolytically.

Accommodation, Ocular↗
PubMed2004

Pro-oxidant activity of zuclopenthixol in vivo: differential effect of the drug on brain oxidative status of scopolamine-treated rats.

Several clinical studies implicated oxidative stress in the pathophysiology of both psychosis and dementia. As dementia is commonly associated with psychosis, antipsychotic medications are of importance in the pharmacotherapy of dementia particularly as a number of antipsychotics were reported to demonstrate neuronal pro-oxidant and/or antioxidant properties. Impairment of learning and memory, as the most characteristic manifestation of dementia, could be induced in experimental animals by acute administration of scopolamine (SCO) with a resultant elevation in brain oxidative status. This study investigated the potential pro-oxidant and/or antioxidant activity of the antipsychotic drug zuclopenthixol acetate, as its effect on brain oxidative status has yet to be evaluated. A 2 x 3 between-subjects factorial design was used to investigate the simultaneous and interactive effects of zuclopenthixol (0.7 and 1.4 mg/kg i.p.) and SCO on rat brain malondialdehyde, glutathione, glutathione peroxidase and superoxide dismutase levels/activities. Results revealed a significant pro-oxidant effect for both zuclopenthixol and SCO alone conditions. In addition, combined treatment of zuclopenthixol and SCO was found to be significantly different compared to either treatment conditions with regard to their effect on different brain oxidative stress indices. Such findings may have valuable implications in the pharmacotherapy of both psychosis and dementia.

Animals↗
PubMed1991

Dose-dependent effects of scopolamine on nocturnal growth hormone secretion in normal adult men: relation to delta-sleep changes.

To explore the sensitivity of nocturnal GH secretion to different degrees of cholinergic blockade, we investigated the effects of two doses of the muscarinic receptor antagonist scopolamine (SCOP; 3.0 and 6.0 micrograms/kg, im) and placebo, administered in a randomized fashion at 2300 h on three nights to eight normal male volunteers. Both doses of SCOP produced significant reductions in mean nocturnal GH concentration compared to the effects of the placebo; the higher dose of SCOP reduced GH to a greater degree than the lower dose, but this difference was not statistically significant (mean, 2.3 micrograms/L after 6 micrograms/kg vs. 3.0 micrograms/L after 3 micrograms/kg). Both SCOP doses significantly shifted GH secretion into later portions of the night, with a significantly greater delay observed after the larger dose. Similarly, a significant delay in the time of the GH rise was produced by SCOP. In contrast, the effects of both doses of SCOP on delta-sleep or sleep onset were small. These data confirm earlier reports demonstrating that cholinergic muscarinic input represents a potentially important source of regulation of nocturnal GH release and suggest that the magnitude of the reduction in GH and the extent of delay in the GH rise time may reflect quantitative differences in the degree of cholinergic blockade. These data are in agreement with recent studies suggesting that the timing of GH release need not be associated with delta-sleep per se.

Adult↗
PubMed2001

Effect of polyacetylenes on the neurite outgrowth of neuronal culture cells and scopolamine-induced memory impairment in mice.

Polyacetylenic alcohols and their linoleates isolated from Panax ginseng C. A. MEYER and Cirsium japonicum DC., of which the lipophilic extracts had been found to affect the neuritogenesis of cultured paraneurons, were demonstrated to have a significant neuritogenic effect on PC12h and Neuro2a cells. Panaxynol and the acetylenic triol in particular were highly efficient at concentrations > or = 2 microm. Panaxynol (20 mg/kg/d, i.p., for 3 d) was confirmed to improve scopolamine-induced memory deficit in mice (Y-maze task). It is suggested that the promotion of neuritogenesis in cultured paraneurons by the addition of panaxynol is related its ability to improve memory deficits in animals.

Acetylene↗
PubMed1993

[A method employing housing in a radial maze apparatus for estimating working memory in mice: effects of scopolamine and delay upon maze performance].

Male ddY mice were housed in a 4-, 6-, or 8-arm radial maze apparatus for 6 hr a day and then removed to a normal cage for fasting until the next day's trial. A water bottle was placed at the central platform. The end of each arm ran to the home cage through a guillotine door (G). Food was placed in the home cage. During the housing in the apparatus, one G was opened, and the remaining Gs were shut. The opened G was changed in random order during the housing period of 6 hr. At the beginning of the trial, all Gs were shut. The mouse was placed on the platform and was permitted to choose the arms until it chose all arms. When the mouse chose the last arm, the G was opened to allow stepping into the home cage. The mice housed in these apparatus learned to go to the home cage without entering already chosen arms within 4-6 days. Scopolamine (0.2 and 0.4 mg/kg, i.p.) impaired the maze performance. A 1- to 4-min delay impaired the performance slightly, but did not show any significant effect depending on the delay intervals. These results suggest that the apparatus is a useful and easy method for estimating working memory and the drug effects thereon in mice.

Animals↗