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PubMed1997

Effects of scopolamine and hippocampal lesions on negative patterning discrimination performance in rats.

Rats were trained in operant chambers to perform an appetitive negative patterning successive discrimination. They were required to respond to the left in response to a tone or click and right to a tone-click compound. Scopolamine and methyl scopolamine impaired performance accuracy and increased response latency and response omissions. Subsequent hippocampal aspiration lesions initially impaired accuracy, which later improved. Lesions decreased response latencies. Finally, the effects of scopolamine and methyl scopolamine were shown to be similar in lesioned and control rats, suggesting that the hippocampus is not involved in the actions of these drugs on this task.

Animals↗
PubMed1981

Transdermal scopolamine in the prevention of motion sickness at sea.

Studies were conducted to evaluate the efficacy of scopolamine, absorbed through intact skin, in preventing motion sickness at sea. Efficacy of transdermal scopolamine was compared with oral dimenhydrinate and placebo. Transdermal applications were made 4 to 16 hr before exposure to motion. Dimenhydrinate or placebo was given 1.5 hr before motion and again 2.5 hr after motion began. Comparison with placebo indicated that transdermal scopolamine provided protection against motion sickness at a significance level of p = 0.0001 and oral dimenhydrinate at a level of p = 0.05. Dry mouth, drowsiness, and blurred vision associated with transdermal scopolamine therapy were minimal.

Adolescent↗
PubMed1999

Regional brain activity during shape recognition impaired by a scopolamine challenge to encoding.

In the present positron emission tomography (PET) study, we examine the effect of a scopolamine-induced challenge to encoding upon the pattern of regional cerebral blood flow during recognition of a list of abstract visual shapes 3 days after encoding of these shapes. This study was conducted to test hypotheses concerning the fusiform and thalamic contributions to object recognition arising from a previous imaging study of impaired recognition. In that study, we demonstrated that activity in the fusiform cortex and the thalamus during shape recognition was modulated by memory challenges. These memory challenges included, on one hand, impaired storage as a consequence of diazepam administration during encoding, and, on the other hand, impaired retrieval caused by a perceptual challenge. Activation in the fusiform cortex decreased during impaired recognition, irrespective of the type of challenge. In contrast, thalamic activation increased only when the recognition deficit resulted from impaired memory storage. Based on these results, we hypothesized that fusiform activation during recognition reflects the matching of an incoming stimulus with a stored one, whereas thalamic activation reflects retrieval attempts. These hypotheses would receive considerable support if scopolamine, which also impairs memory storage, induced similar modulations of fusiform and thalamic activation. In the present study, we observed that a scopolamine challenge to encoding does indeed modulate the activity in the very same regions that were previously modulated by a diazepam challenge. Hence, a similar memory deficit, although primarily effected through different neurochemical pathways, was paralleled by a similar modulation of activity in the same set of nodes in the shape recognition network. In the fusiform cortex, scopolamine decreased recognition-related activity, as did the sensory challenge of retrieval. Furthermore, covariate analysis demonstrated that the level of fusiform activity linearly correlates with behavioural performance. In the thalamus, activation increased following impaired encoding. This is in accordance with the idea that enhanced thalamic activity reflects increased effort expended in retrieval. In addition, in the intraparietal sulcus, differential activation also increased following impaired memory storage, possibly reflecting enhanced visuospatial attention in an effort to compensate for impaired performance.

Administration, Oral↗
PubMed2003

Ninjin-yoei-to (Ren-Shen-Yang-Rong-Tang) and Polygalae radix improves scopolamine-induced impairment of passive avoidance response in mice.

We investigated the effect of Ninjin-yoei-to (Ren-Shen-Yang-Rong-Tang), a Japanese herbal medicine, and found that 1000 mg/kg p.o. improved the scopolamine-induced impairment of passive avoidance response in mice. Further, the same dose of Ninjin-yoei-to enhanced oxotremorine-induced tremors in mice. The water extract of Polygalae radix, one of the constituent herbs of Ninjin-yoei-to, at a dose of 100 mg/kg significantly improved the scopolamine-induced impairment of passive avoidance response and enhanced oxotremorine-induced tremors in mice. Moreover, the enhancement of oxotremorine-induced tremors by Ninjin-yoei-to (1000 mg/kg) and Polygalae radix (100 mg/kg) was completely antagonized by pretreatment of scopolamine hydrobromide (0.5 mg/kg). These results suggest that Ninjin-yoei-to may improve the scopolamine-induced impairment of passive avoidance response by enhancing the cholinergic system and that Polygalae radix may be involved in the action of Ninjin-yoei-to.

Administration, Oral↗
PubMed2002

Effects of excitotoxic median raphe lesions on scopolamine-induced working memory deficits in inhibitory avoidance.

The aim of the present study was to investigate the effects of excitotoxic damage of the serotonergic cell bodies in the median raphe nucleus (MRN) on the scopolamine-induced working memory deficits in a single-trial light/dark inhibitory avoidance task. Rats were given 1 mg/kg of scopolamine hydrobromide (intraperitonal, i.p.) or saline before the inhibitory avoidance training, in which initial preference to the dark compartment (escape latency) was used to measure nonmnemonic behaviors, and response latency to enter the dark compartment immediately after the shock was used to measure working memory. It was found that scopolamine significantly reduced escape latencies in sham-lesioned rats, whereas it had no effect in the rats with MRN lesions. Although MRN lesion per se did not alter response latency, it prevented scopolamine-induced decrease in this parameter. These results suggest that the antagonistic interactive processes between serotonergic projections of the MRN and the muscarinic cholinergic system modulate nonmnemonic attentional component of working memory formation in the inhibitory avoidance.

Alzheimer Disease↗
PubMed1988

The effects of scopolamine and traumatic brain injury on central cholinergic neurons.

This study examined the effects of scopolamine and fluid percussion traumatic brain injury (TBI) on the activity of cholinergic neurons in specific areas of the rat brain 12 min, 4 h, and 24 h after injury. Acetylcholine (ACh) turnover, used as an index of cholinergic neuronal activity, was determined using gas chromatography-mass fragmentography. Scopolamine pretreatment prevented significant increases in dorsal pontine ACh turnover at 12 min and 4 h after TBI, suggesting that the drug's protective actions against the neurologic deficits following TBI may involve blockade of cholinergic neuronal activation as well as postsynaptic muscarinic blockade. The responses of thalamic, hippocampal, and amygdaloid cholinergic neurons to TBI did not differ substantially in scopolamine-pretreated rats from those studied previously in untreated fluid-percussion-injured rats. However, cholinergic neurons in the cingulate-frontal cortex of rats receiving TBI did respond in a different manner to scopolamine than those of rats receiving sham injury, suggesting a disruption of regulation of cortical cholinergic neurons following this model of TBI.

Acetylcholine↗
PubMed2003

No influence of scopolamine hydrobromide on odor detection performance of rats.

Despite speculation that the muscarinic cholinergic antagonist, scopolamine, may influence the olfactory sensitivity of rats, there have been no definitive studies on this point to date. In this study, we examined the influence of a range of doses of scopolamine hydrobromine (namely, 0.10, 0.125, 0.15 and 0.20 mg/kg i.p.) on the odor detection performance of 15 adult male Long-Evans rats to ethyl acetate. Air-dilution olfactometry and a go/no-go operant signal detection task were employed. The drug conditions and a saline control were administered to each animal in an order counterbalanced by Latin squares, with 2 day intervals interspersed between tests. Scopolamine had no significant influence on odor detection performance per se, as measured by percent correct S+ and S- responses and a non-parametric signal detection measure of sensitivity. This is in contrast to the relatively large effects previously observed in the same test paradigm for such drugs as the D-1 agonist SKF 38393 and the D-2 agonist quinpirole. These data suggest that scopolamine has no meaningful influence on a well-practiced odor detection task.

Aging↗
PubMed2006

Testing for atropine and scopolamine in hair by LC-MS-MS after Datura inoxia abuse.

Datura inoxia belongs to the family of Solanaceae. This is a very common plant in New Caledonia that contains two main toxic alkaloids, l-atropine and l-scopolamine. In this study, we report the case of a 20-year-old male admitted to an Emergency Unit after consumption of 6 dried flowers in hot water for hallucinations, mydriasis, and agitation associated with tachycardia and increase of systolic blood pressure to 180. Full recovery was observed after one week. Three weeks later, a lock of about 80 hairs (200 mg) was collected from the subject in vertex posterior with scissors to be tested for both atropine and scopolamine. After decontamination with dichloromethane, a strand of hair was segmented into three parts, cut into small segments (< 1 mm), incubated overnight in 1 mL pH 8.4 phosphate buffer in the presence of 2.5 ng atropine-d(3), the internal standard, then extracted with 5 mL dichloromethane/isopropanol/n-heptane (50:17:33). The residue was reconstituted in 100 microL of methanol, from which 10 microL was injected into an XTerra MS C18 column (100 x 2.1 mm, 3.5 microm) eluted with a gradient of acetonitrile and formate buffer delivered at a flow rate of 0.2 mL/min. A Quattro Micro triple-quadrupole mass spectrometer (MS) was used for analyses. Ionization was achieved using electrospray in the positive ionization mode. For each compound, detection was related to two daughter ions (atropine: m/z 290.2 to 124.0 and 92.9; atropine-d(3): m/z 293.1 to 127.0 and 92.9; scopolamine: m/z 304.1 to 138.0 and 156.0). Although atropine was never detected (limit of detection = 2 pg/mg), scopolamine was identified in the three segments, in the range 14 to 48 pg/mg. The absence of atropine in hair is consistent with its very low dosage in the flower of Datura inoxia. Hair segmentation indicated that the subject was previously exposed on several occasions to the plant. Liquid chromatography-tandem MS appears to be a necessity for testing tropane alkaloids of the Datura group, given the low concentrations to be measured.

Adult↗
PubMed1976

Amnesic actions of diazepam and scopolamine in man.

In man, diazepam alone and in combination with scopolamine interferes with the memory of visual and painful stimuli. With a 15-minute interval between injection of the drug and the showing of emotionally neutral pictures, scopolamine (0.5 mg/70 kg) produces 14 per cent forgetting when evaluated 24 hours later. Under these conditions diazepam (10 mg/70 kg) produces 41 per cent forgetting, while the combination causes 64 per cent. Under conditions designed to insure selection of subjects in whom registration was clearly quite intact at the time of the initial exposure to the pictures, memory was still found to be impaired when tested 24 hours later. Graded doses of diazepam to as much as mg/70 kg in combination with 0.5 mg/70 kg scopolamine produced a virtually linear dose-response curve for amnesia. These results are compatible with the interpretation that the diazepam-scopolamine mixture interferes with memory by blocking consolidation of the memory trace.

Adolescent↗
PubMed1993

Interleukin-2 enhances scopolamine-induced amnesia and hyperactivity in the mouse.

We studied the effects of human recombinant interleukin-2 (IL-2) on scopolamine-induced amnesia for a passive avoidance response and on scopolamine-induced hyperactivity, in the mouse. The pre-training intraperitoneal administration of the cytokine significantly enhanced the amnesic effect of scopolamine (1.0 mg kg-1 i.p.). Similar effects were observed after repeated administration (2,500 IU/mouse i.p. for 10 days) of the cytokine. In this condition, the treatment with the pro-cholinergic drug acetylcarnitine completely blocked the pro-amnesic effect of IL-2. The cytokine did not affect plasma glucose concentrations, nor induced any change in footshock sensitivity. Intraperitoneal injection of IL-2 significantly enhanced the scopolamine-induced hyperactivity, whereas the cytokine alone was ineffective in modifying locomotor activity. Our results suggest an involvement of the cholinergic system in the neuromodulatory action of IL-2.

Amnesia↗
PubMed1994

Ondansetron fails to attenuate a scopolamine-induced deficit in a Stone maze task.

The 5-HT3 receptor antagonist ondansetron has previously been reported to improve cognition in the mouse, rat and marmoset in a variety of behavioural paradigms. The present study used the Stone maze to test the effect of ondansetron on the deficit caused by scopolamine in the performance of a highly complex spatial memory task in the rat. Ondansetron administered over a large dose range (1.0 ng kg-1-1.0 micrograms kg-1, i.p., b.d.) for a period of 10-15 days failed to attenuate the scopolamine deficit. Indeed at one dose level ondansetron (100 ng kg-1, i.p., b.d.) administered in combination with scopolamine (0.5 mg kg-1, i.p.) significantly potentiated the deficit, compared with the performance of rats receiving scopolamine alone.

Animals↗
PubMed2001

Evaluation of transdermal scopolamine as treatment for acquired nystagmus.

We conducted an unmasked evaluation of transdermal scopolamine in seven patients with acquired nystagmus for whom other treatments had been unsatisfactory. We measured eye speed and visual acuity before and several hours after starting treatment. Median eye speed decreased slightly in three patients but increased in two; no change in visual acuity occurred in any patient. One patient was unable to tolerate the side effects of scopolamine after two hours, but the others continued the scopolamine treatment for 48 hours; only one reported minor improvement. We conclude that transdermal scopolamine is not likely to be an effective treatment of acquired nystagmus. Patients should be monitored during the first few hours of treatment to determine whether vision is improved or made worse and whether side effects occur.

Administration, Cutaneous↗
PubMed2000

Chlorpyrifos-induced hypothermia and vasodilation in the tail of the rat: blockade by scopolamine.

Organophosphate pesticides such as chlorpyrifos reduce core temperature (Tc) in laboratory rodents. The mechanism(s) responsible for the chlorpyrifos-induced hypothermia are not well known. This study assessed the role of a key effector for thermoregulation in the rat, vasomotor control of heat loss from the tail, and its possible cholinergic control during chlorpyrifos-induced hypothermia. Tc and motor activity were monitored by telemetry in female Long-Evans rats maintained at an ambient temperature (Ta) of 25 degrees. Tail skin temperature (Tsk(t)) was measured hourly. Rats were dosed with chlorpyrifos (0 or 25 mg/kg orally). Two hr later the rats were dosed with saline or scopolamine (1.0 mg/kg intraperitoneally). Two hr after chlorpyrifos treatment there was a marked elevation in Tsk(t)) concomitant with a 0.5 degrees reduction in Tc. Scopolamine administered to control rats led to a marked elevation in Tc with little change in Tsk(t). Rats treated with chlorpyrifos and administered scopolamine underwent a marked vasoconstriction and elevation in Tc. Vasodilation of the tail is an important thermoeffector to reduce Tc during the acute stages of chlorpyrifos exposure. The blockade of the response by scopolamine suggests that the hypothermic and vasodilatory response to chlorpyrifos is mediated via a cholinergic muscarinic pathway in the CNS.

Analysis of Variance↗
PubMed1985

Comparison of rectal diazepam and subcutaneous morphine-scopolamine administration for outpatient sedation in minor oral surgery.

In a randomized cross-over study on sedation in outpatient oral surgery, subcutaneous administration of morphine-scopolamine was compared with rectal administration of diazepam. The mean dose of morphine was 0.13 mg kg-1 (range 0.13-0.24) and of diazepam 0.57 mg kg-1 (range 0.50-0.71). Apprehension, the determining factor for patients' preference for sedation method, the recovery from sedation and the postoperative course were studied. Both methods produced the desired effects. For diazepam, the effect was scored higher by the patient than the nurse observer and for morphine-scopolamine the opposite was found. Postoperative pain and patients' preference for sedation did not differ between the methods and the determining factor for the patients' preference for sedation method was the experience of stronger tranquilization. Side-effects such as prolonged recovery, nausea, dizziness, and dysphoria were frequent during the postoperative course after the morphine-scopolamine sedation but were not seen during diazepam sedation. Thus, rectal administration of diazepam should be preferred to morphine and scopolamine for sedation in minor oral surgery performed under local anesthesia.

Adolescent↗
PubMed1995

Premedication with promethazine and transdermal scopolamine reduces the incidence of nausea and vomiting after intrathecal morphine.

Intrathecal morphine provides effective postoperative pain relief in major orthopaedic surgery. In use, however, is associated with unpleasant side effects like nausea and vomiting. The effect of different premedications on postoperative emetic sequelae induced by intrathecal morphine was studied in a prospective, double blind study. Sixty patients scheduled for arthroplasty surgery of the lower extremity were anaesthetized with spinal anaesthesia with a combination of isobaric bupivacaine 20 mg and morphine 0.3 mg. For premedication the patients were randomised to three groups of equal size. They received either oral diazepam (5-15 mg), oral promethazine (10 mg) or a combination of promethazine and transdermal scopolamine (1.5 mg). Sixty percent of the patients with both promethazine and transdermal scopolamine were totally free from postoperative nausea and vomiting (PONV) symptoms compared to those premedicated with diazepam (40%) or promethazine alone (30%). Promethazine together with transdermal scopolamine reduced significantly the number of patients with vomiting (to 25%) and also vomiting episodes. This combination was also more efficient in reducing the incidence of nausea (to 25%) and nausea episodes than promethazine along (P < 0.05). Combination also reduced the requests for additional pain relief (P < 0.05). PONV occurred in a majority of patients during the first 12 hours of the 24 hour study period and the need for additional analgesics thereafter. The incidence of itching (50-65%) and urinary catheterisation (55-70%) was similar in all groups. In conclusion, the combination of oral promethazine and transdermal scopolamine was most effective in reducing PONV symptoms and also reduced the need for postoperative pain treatment.

Administration, Cutaneous↗
PubMed1986

Non-muscarinic effects of scopolamine on N1E-115 neuroblastoma cells.

Membrane effects of scopolamine on N1E-115 neuroblastoma cells were studied using intracellular recording techniques. Scopolamine in concentrations of 50 nM-1 microM induced a depolarization together with a decreased cell input resistance. This response had a reversal potential at +10 to +20 mV in a medium with normal sodium concentration (146.5 mM), and a reversal potential around -10 mV when the sodium concentration in the medium was lowered to 80 mM. The scopolamine-induced depolarization could not be blocked by carbachol (100 microM), and had a reversal potential at +10 to +20 mV. The simplest explanation of the results obtained is that scopolamine increases the membrane permeability for sodium and potassium, in a manner which is not related to muscarinic cholinergic receptors.

Animals↗
PubMed1988

Effects of physostigmine and scopolamine on long-term potentiation of hippocampal population spikes in rats.

To elucidate an involvement of the cholinergic system in the long-term potentiation phenomenon, effects of physostigmine and scopolamine on population spike and its long-term potentiation in the dentate granule cell layer of anesthetized rats and in the CA1 pyramidal cell layer of rat hippocampal slices were examined. In anesthetized rats, physostigmine (0.01 mg/kg, i.v.) enhanced at a late phase the long-term potentiation induced by tetanic stimulation (15 Hz, 15 s, 7.5 times the threshold for population spike) of the perforant path, while scopolamine (1.0 mg/kg) suppressed it at an early phase. The two drugs did not affect the population spike itself. The time course of the long-term potentiation under the treatment of physostigmine was similar to that induced by stronger tetanic stimulation (10 times the threshold). In hippocampal slices, physostigmine (10(-6)M) showed a tendency to enhance the long-term potentiation induced by tetanic stimulation (15 Hz, 15 s, 5 times the threshold) of the stratum radiatum, with an increase of the population spike itself. Scopolamine (10(-5)M) markedly suppressed the long-term potentiation with a decrease of the population spike itself. From these results, it is suggested that cholinergic modification by physostigmine or scopolamine affects the long-term potentiation phenomenon in the hippocampus under the in vivo and in vitro conditions.

Animals↗
PubMed1999

The effects of scopolamine on changes in regional cerebral blood flow during classical conditioning of the human eyeblink response.

We examined the effects of scopolamine on the functional anatomy of classical conditioning of the human eyeblink response. Ten healthy young normal female volunteers (mean age +/- SEM: 26.7 +/- 0.9 years) were administered 0.4 mg scopolamine intravenously 1 h before regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) and H215O. Scans occurred during three sequential phases: (1) explicitly unpaired presentations of the unconditioned stimulus (airpuff to the right eye) and conditioned stimulus (binaural tone), (2) paired presentations of the two stimuli (associative learning) and (3) explicitly unpaired presentation of the stimuli (extinction phase). Scopolamine impaired acquisition of the conditioned eyeblink response (54.7 +/- 4.9%) relative to 18 untreated subjects from two previous PET studies. Regions that showed significant relative increases in rCBF during conditioning included the right lateral occipital cortex, the right inferior occipital cortex, the right lateral temporo-occipital cortex, the left medial temporo-occipital cortex, the posterior cingulate, the right cerebellum/brain stem area and the medial cerebellum. Significant relative decreases in rCBF were measured in the thalamus, the left putamen/insula area, the right putamen and the left and middle cerebellar cortex. The data partially replicate previous findings in unmedicated young volunteers of conditioning-specific rCBF changes in the cingulate cortex, the cerebellar cortex, the insula and the lateral temporo-occipital cortex. Our finding of decreased rCBF in the thalamus and increased rCBF in the occipital cortex may be attributable to effects of scopolamine per se rather than conditioning. Our data lend further support to the notion that classical conditioning involves distributed changes in multiple systems within the central nervous system.

Acoustic Stimulation↗