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PubMed1996

Effects of ventral hippocampal galanin on spatial learning and on in vivo acetylcholine release in the rat.

The neuropeptide galanin coexists in the medial septum and diagonal band of Broca with a population of acetylcholine neurons which project mainly to the ventral hippocampus. The present studies investigated the role of ventral hippocampal galanin in spatial learning in the male rat using a spatial learning task. In addition, the effects of galanin on cholinergic function were monitored by in vivo microdialysis and high-performance liquid chromatography. Bilateral microinjections of galanin (3 nmol/ rat) via chronic cannulae placed into the ventral hippocampus (i.v.h.) produced a slight but significant impairment of acquisition of the spatial task, while the 1 nmol dose of galanin facilitated acquisition. The 6 nmol dose of galanin failed to affect performance. A trend for an impairment of long-term memory retention (examined seven days after the last training session) was observed after 3 nmol of galanin, while the 1 nmol dose facilitated retention performance. Scopolamine (0.1 mg/kg, s.c.) caused a marked impairment of acquisition. Galanin (3 nmol/rat) given i.v.h. failed to modify the acquisition impairment caused by scopolamine (0.1 mg/kg, s.c.). These results suggest that galanin given i.v.h. produces a biphasic dose-dependent effects on spatial learning. In freely moving rats, galanin (3 nmol/10 microliters) given into the lateral ventricle (i.c.v.) did not affect basal acetylcholine release. In contrast, perfusion (100 min) with galanin (0.1 or 0.3 nmol/1.25 microliters/min) through the ventral hippocampal probe resulted in a reduction of basal acetycholine release which was dose-dependent and reversible. Galanin given i.c.v. (3 nmol/10 microliters) or through the probe (0.3 nmol/1.25 microliters/min) attenuated the increase in acetylcholine release evoked by the muscarinic antagonist scopolamine (0.1 mg/kg, s.c.; 0.001 nmol/1.25 microliters/min through the probe). The galanin plus scopolamine combinations produced a 50% lower increase in the extracellular acetylcholine concentrations than scopolamine alone. This suggests that the mechanism(s) behind scopolamine- and galanin-induced stimulation of acetylcholine differ. These results indicate that ventral hippocampal galanin plays a role in cognition and that it has a powerful and modulatory effect on cholinergic transmission. However, the effects of exogenous galanin on spatial learning cannot be directly related to changes in in vivo cholinergic transmission in the ventral hippocampus. These discrepancies may relate to effects on subtypes of galanin receptors with different functional coupling. In addition, other hippocampal neurotransmitter systems (e.g. noradrenergic neurons) important for cognitive functions may also be modulated by ventral hippocampal galanin.

Acetylcholine↗
PubMed2004

The T-maze continuous alternation task for assessing the effects of putative cognition enhancers in the mouse.

The T-maze continuous alternation task (T-CAT) assesses the spatial exploratory performance in mice. We performed a series of four experiments in order to establish the T-CAT in mice in our laboratory, to replicate published findings, and to investigate the effects of scopolamine and donepezil. In the first experiment, the task was found to be sensitive to differences between mouse strains, corroborating findings reported by Gerlai. HsdWin:CFW1 mice alternated below chance level, C57BL/6JIco and B6D2F1/JIco mice performed above chance level, and C57BL/6NTac and 129S6/SvEvTac mice performed at chance level. In the second experiment, donepezil (Aricept, E2020) at the dose of 3 mg/kg p.o. increased the rate of alternations above the level of the vehicle-treated control group in C57BL/6JIco mice, suggesting that this drug can act as cognition enhancer in normal animals. 1mg/kg scopolamine, administered intraperiteoneally (i.p.), impaired the spontaneous alternation behaviour of the mice. The slightly lower dose of 0.75 mg/kg did not affect alternation performance. The high dose of donepezil (3 mg/kg) was able to antagonise the scopolamine-induced performance deficit. With respect to time to complete a session, the results were inconclusive. In the third experiment, we found that scopolamine, administered i.p. at the dose of 1 mg/kg, or subcutaneously (s.c.) at the dose of 0.1 mg/kg, decreased the rate of spontaneous alternations in C57BL mice in the T-CAT and increased the time to complete a session. Most likely due to adverse side effects induced by the dose of 1mg/kg scopolamine, 4 out of 10 animals did not complete at least eight free-choice trials during the maximum session duration of 30min. No such adverse effects were seen after 0.1 mg/kg scopolamine, administered s.c. Finally, we evaluated whether the T-CAT yields replicable results. We conclude that the T-CAT provides a reliable tool for assessing the effects of cognition-modulating treatments in mice.

Analysis of Variance↗
PubMed1982

Age-dependent improvement in passive avoidance learning of the young chick: cholinergic mediation?

Cholinergic mediation of the age-dependent improvement in response suppression of the young chick was studied by determining the performance of 4-day-old chicks, pretreated with scopolamine, during passive avoidance (PA) and extinction testing. In Experiment 1, chicks were trained briefly to key peck for heat reward (prepunishment training), and then tested for PA learning under immediate, 2-sec-delayed, or no shock condition. Half of the chicks in each wing-shock (5 mA, 5 sec) condition received saline injections before prepunishment training and .5 mg/kg scopolamine injections after prepunishment training. The rest of the chicks received .5 mg/kg scopolamine injections both before and after prepunishment training. For chicks in both scopolamine groups, delaying shock onset resulted in significantly less response suppression than immediate response-contingent shock. In Experiment 2, 4-day-old chicks injected with either saline or scopolamine were trained to key peck for heat reward and then tested for resistance to extinction under either response-contingent shock or nonshock conditions. Punishment decreased the number of extinction responses for both saline and scopolamine groups of chicks. Previous studies have shown that normal 1-day-old chicks do not show a significant delay of punishment effect during PA testing and that response-contingent punishment increases the number of their responses during extinction. Hence, the results of the present experiments indicate that the age-dependent improvement in response suppression of the young chick cannot be explained solely by a significant increase in central cholinergic functioning.

Aging↗
PubMed2000

Cholinergic agents and the McCollough effect.

The strength of the McCollough effect (ME), a pattern-contingent colour aftereffect, has been shown to be inversely related to acetylcholine, being significantly strengthened by (anticholinergic) scopolamine and weakened by (cholinergic) physostigmine delivered before adapting to the ME stimuli. The purpose of the present study was (i) to establish whether the effect of pre-adaptation scopolamine is linearly dose-dependent and (ii) to investigate the effects of scopolamine and physostigmine delivered between adaptation and testing. In experiment 1, ten healthy male volunteers who received placebo, or 0.6 mg, 1.2 mg, or 1.8 mg scopolamine before adapting to ME stimuli showed a significant linear dose-dependence over tests repeated from 10 to 70 min after adaptation. In experiment 2 twelve male volunteers adapted to ME stimuli and then received placebo, 1.2 mg oral scopolamine, or 0.75 mg subcutaneous physostigmine. On subsequent repeated testing, strength of the ME was increased by scopolamine and decreased by physostigmine relative to placebo. Both experiments were double-blind double-dummy repeated measures. These data support the view that the ME is a product of inhibitory mechanisms in the visual system rather than processes involved in associative learning.

Adult↗
PubMed1988

In vivo probe of central cholinergic systems.

Age-related cognitive impairments and dementia of Alzheimer type have been linked to alterations in the cholinergic system. In the present study, evoked potentials and neuropsychological testing were obtained in healthy subjects during neuropharmacological manipulations including: scopolamine (anticholinergic), scopolamine plus physostigmine (anticholinesterase), scopolamine plus methylphenidate (adrenergic), and placebo. Scopolamine prolonged P3 latency and reduced spectral power of long latency evoked potentials without significantly altering earlier components. Physostigmine partially reversed these effects, but methylphenidate did not. Motor speed was slowed by scopolamine, but not by scopolamine plus methylphenidate. Cholinergic systems appear to be involved in generation or modulation of the P3 potential, possibly secondary to the cholinergic role in selective attention. Similar techniques may be useful as in vivo probes of central cholinergic function and thus as research and diagnostic aids in aging and disease.

Adult↗
PubMed2000

Muscarinic cholinergic modulation of prepulse inhibition of the acoustic startle reflex.

The purpose of the present study was to determine the effects of muscarinic cholinergic receptor antagonists and agonists on prepulse inhibition (PPI) of the acoustic startle reflex in rats. The muscarinic receptor antagonist scopolamine (0.03-1.0 mg/kg) produced a significant dose-dependent decrease in PPI without affecting startle amplitude. In contrast, N-methyl scopolamine, the quaternary analog of scopolamine, had no effect on PPI, indicating that scopolamine disrupted PPI through a central cholinergic mechanism. Two other muscarinic receptor antagonists, trihexyphenidyl (0.3-10 mg/kg) and benztropine (0.03-10 mg/kg), produced significant decreases in PPI similar to scopolamine. On the other hand, the muscarinic receptor antagonists dicyclomine (0.03-10 mg/kg) and biperiden (0.03-10 mg/kg) had no effect on PPI but significantly decreased startle amplitude. Mecamylamine (0.1-10 mg/kg), a nicotinic receptor antagonist, also had no effect on PPI. Administered alone, the muscarinic receptor agonists pilocarpine (0. 03-10 mg/kg), oxotremorine (0.01-0.3 mg/kg), RS-86 (0.1-3.0 mg/kg), and arecoline (0.3-10 mg/kg), as well as the cholinesterase inhibitors physostigmine (0.01-0.3 mg/kg) and tacrine (0.03-10 mg/kg), had no effect on PPI, but each produced significant decreases in startle amplitude at the highest doses tested. In addition, the disruption of PPI by scopolamine was reversed in a dose-dependent manner by the muscarinic receptor agonist oxotremorine. The present findings demonstrate that the muscarinic cholinergic system plays an important role in the normal mechanisms of PPI.

Acoustic Stimulation↗
PubMed2000

Cholinergic neuronal modulation alters dopamine D2 receptor availability in vivo by regulating receptor affinity induced by facilitated synaptic dopamine turnover: positron emission tomography studies with microdialysis in the conscious monkey brain.

To evaluate the cholinergic and dopaminergic neuronal interaction in the striatum, the effects of scopolamine, a muscarinic cholinergic antagonist, on the striatal dopaminergic system were evaluated multi-parametrically in the conscious monkey brain using high-resolution positron emission tomography in combination with microdialysis. l-3,4-Dihydroxyphenylalanine (l-[beta-(11)C]DOPA) and 2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane ([beta-(11)C]CFT) were used to measure dopamine synthesis rate and dopamine transporter (DAT) availability, respectively. For assessment of dopamine D(2) receptor binding in vivo, [(11)C]raclopride was applied because this labeled compound, which has relatively low affinity to dopamine D(2) receptors, was hypothesized to be sensitive to the striatal synaptic dopamine concentration. Systemic administration of scopolamine at doses of 10 and 100 microg/kg dose-dependently increased both dopamine synthesis and DAT availability as measured by l-[beta-(11)C]DOPA and [beta-(11)C]CFT, respectively. Scopolamine decreased the binding of [(11)C]raclopride in a dose-dependent manner. Scopolamine induced no significant changes in dopamine concentration in the striatal extracellular fluid (ECF) as determined by microdialysis. However, scopolamine dose-dependently facilitated the striatal ECF dopamine induced by the DAT inhibitor GBR12909 at a dose of 0.5 mg/kg. Scatchard plot analysis in vivo of [(11)C]raclopride revealed that scopolamine reduced the apparent affinity of dopamine D(2) receptors. These results suggested that the inhibition of muscarinic cholinergic neuronal activity modulates dopamine turnover in the striatum by simultaneous enhancement of the dynamics of dopamine synthesis and DAT availability, resulting in no significant changes in apparent "static" ECF dopamine level but showing a decrease in [(11)C]raclopride binding in vivo attributable to the reduction of affinity of dopamine D(2) receptors.

Animals↗
PubMed1986

The effect of antimotion sickness drugs on habituation to motion.

The effect of antimotion sickness drugs on habituation was studied. Subjects were rotated once a day for 5 d to the malaise III end-point after receiving placebo, 1 mg scopolamine, 10 mg d-amphetamine, or the combination of 0.6 mg scopolamine with 5 mg of d-amphetamine. The placebo scores had a Spearman coefficient of correlation of 0.88 with the initial untreated tests. This demonstrated a high reliability for the M-III end-point and that little habituation resulted from the test design. The combination of 0.6 scopolamine with 5 mg amphetamine produced the fastest rate of habituation closely followed by the dose of 1 mg scopolamine. 10 mg of d-amphetamine also produced an increase in habituation over placebo scores. When the medications were discontinued on day 5 a rebound in sensitivity to vestibular stimulation occurred with scopolamine and scopolamine with d-amphetamine. The increased habituation appears to be due to the greater exposure to vestibular stimulation permitted by the medications.

Adolescent↗
PubMed1993

Comparative behavioral and neurochemical activities of cholinergic antagonists in rats.

The comparative behavioral and neurochemical activities of the muscarinic cholinergic antagonists scopolamine, trihexyphenidyl and pirenzepine, and the nicotinic cholinergic antagonist mecamylamine were evaluated in rats. The three muscarinic antagonists, but not the nicotinic antagonist, impaired memory performance in a spatial alternation task. The minimal effective doses required to disrupt behavior were 0.03, 1.0 and 10 mg/kg for scopolamine, trihexyphenidyl and pirenzepine, respectively. Scopolamine and trihexyphenidyl inhibited ex vivo binding of [3H] pirenzepine to M1 receptors in cerebral cortex, indicating ready penetration into the brain. In contrast, pirenzepine penetrated into the brain at relatively high doses, suggesting poor penetration into the brain. Scopolamine and trihexyphenidyl, but not pirenzepine, inhibited [3H]quinuclidinyl benzilate binding to brain stem M2 receptors ex vivo after subcutaneous administration. In addition, scopolamine and trihexyphenidyl, but not pirenzepine, decreased acetylcholine (ACh) levels in striatum and hippocampus, presumably by increasing ACh release by blocking ACh feedback inhibition at M2 receptors. Scopolamine and trihexyphenidyl also produced modest decreases in levels of the dopamine metabolite 3,4-dihydroxyphenylacetic acid in striatum, most likely due to blockade of M1 heteroreceptors on dopamine nerve terminals. The present results are consistent with the interpretation that muscarinic antagonists impair memory performance in rats, at least in part, by blocking M1 muscarinic receptors. The present results do not support a role for blockade of M2 receptors. Further research is needed to determine the extent to which blockade of other (M3, M4, M5) muscarinic receptor subtypes contributes to the memory-impairing effects of muscarinic cholinergic antagonists.

Acetylcholine↗
PubMed1996

Interactions between D1 and muscarinic receptors in the induction of striatal c-fos in rats depleted of dopamine as neonates.

The contributions of striatal D1 receptors to the expression of sensorimotor behavior are qualitatively different in rats depleted of dopamine (DA) as neonates vs. as adults. In an effort to reveal neuronal mechanisms underlying these behavioral difference we determined the effects of the partial D1 agonist SKF 38393, the muscarinic antagonist scopolamine, and the combination of the two drugs on the induction of c-fos in the striatum and its projection sites, the globus pallidus and substantia nigra. Adult rats, given intracerebroventricular injections of 6-hydroxydopamine (6-OHDA, 50 micrograms/5 microliters/hemisphere) or its vehicle on postnatal day 3, were treated with SKF 38393 (1.5 mg/kg, i.p.), scopolamine (5.0 mg/kg, i.p.) or the combination of the two drugs. There was no significant induction of c-fos in vehicle-treated controls, regardless of drug administration. In DA-depleted rats, scopolamine also did not induce c-fos whereas SKF 38393 produced a significant increases in the number of FOS-positive cells in the dorsal, but not ventral, striatum. The combined administration of scopolamine and SKF 38393 resulted in a potent synergism in the number of FOS-positive cells in DA-depleted rats. These interactions between lesion condition and drugs on c-fos induction were not secondary to differences in drug-induced behavioral activity. Activity levels were no different in vehicle vs. DA-depleted rats following the combined administration of scopolamine + SKF 38393, yet the two groups of rats exhibited marked differences in the density of FOS-positive striatal neurons. The effects of scopolamine and SKF 38393 on c-fos induction in striatum are qualitatively similar to those reported in rats DA-depleted as adults and suggest that, at this single-label level of analysis, the ability of D1 and muscarinic receptors to influence striatal activity does not contribute to the marked age-related differences in the behavioral effects of DA depletions.

Animals↗
PubMed1986

Distinct sites of functional interaction between dopamine, acetylcholine and gamma-aminobutyrate within the neostriatum: an electromyographic study in rats.

In order to study the functional interaction between dopamine, acetylcholine and gamma-aminobutyrate within the rat neostriatum, we investigated the effect of intrastriatal injection of different drugs acting on these transmitter systems on muscle tone measured as tonic activity in the electromyogram of the gastrocnemius muscle. Bilateral injection of haloperidol (500 ng) into the rostral neostriatum (rostral injection: A8920-9650(46] induced tonic activity in the electromyogram, whereas injection into the intermediate part (intermediate injection; A7020-7890(46] was ineffective. Muscimol (25 ng) induced tonic activity in the electromyogram, when injected into the intermediate part and not into the rostral part, while bethanechol (1 microgram) was effective when injected into either site. Haloperidol-induced tonic activity in the electromyogram was prevented by coadministration of apomorphine (500 ng) or scopolamine (1 microgram), but not of bicuculline (300 ng). Haloperidol-induced tonic activity in the electromyogram was also reduced by subsequent intermediate injection of scopolamine or bicuculline, while apomorphine was ineffective. Tonic activity in the electromyogram induced by rostral injection of bethanechol was prevented by coadministration of scopolamine, but not of apomorphine. Intermediate injection of scopolamine or bicuculline reduced the tonic activity in the electromyogram after rostral or intermediate injection of bethanechol. Tonic activity in the electromyogram induced by intermediate injection of muscimol was prevented by coadministration of bicuculline, but not of scopolamine. Rostral injection of apomorphine or scopolamine failed to alter the tonic activity in the electromyogram induced by intermediate injection of bethanechol or muscimol. These results point to the existence of: a functional interaction between dopamine and acetylcholine in the rostral neostriatum; a functional interaction between acetylcholine and gamma-aminobutyrate in the intermediate neostriatum, and a functional flow of information from the rostral to the intermediate neostriatum.

Acetylcholine↗
PubMed2001

Tropane alkaloid production by shoot culture of Duboisia myoporoides R. Br.

This work demonstrates the presence of hyoscyamine and scopolamine at different stages of shoot regeneration from non-organogenic and organogenic calli. The 11-week-old non-organogenic calli contained 0.41+/-0.03 and 0.23+/-0.02 microg g(-1) dry wt hyoscyamine and scopolamine respectively. However, no root meristem was found in the calli. The alkaloids were absent in 2-week-old organogenic calli. The shoot-buds induced on the non-organogenic and organogenic calli did not contain these alkaloids. Hyoscyamine and scopolamine contents of the 6-week-old non-rooted shoots regenerated from non-organogenic calli were 7.8+/-0.1 and 6.5+/-0.4 microg g(-1) dry wt respectively and those in the 9-week-old non-rooted shoot regenerated from organogenic calli were 38.5+/-0.4 and 3.6+/-0.1 microg g(-1) dry wt respectively. Hyoscyamine and scopolamine contents of the 4-week-old roots regenerated from non-organogenic and organogenic calli were higher than those in the non-rooted shoots. Since the presence of hyoscyamine and scopolamine in the non-rooted shoot depends on the stage of differentiation, manipulation of culture environment may improve hyoscyamine and scopolamine contents of the non-rooted shoots.

Alkaloids↗
PubMedDate not supplied

Toxicological evaluation of the staircase test for assessing fine motor movements.

A variety of tests have been developed to study neurotoxicant-related changes in motor function. However, despite recent advances, there remains a need for simple and specific tests of fine motor movements. Accordingly, we chose to evaluate whether a method developed for measuring changes in skilled movements following motor pathway lesions in rodents would provide a sensitive, specific, and economical approach to assessing fine motor control in the toxicology laboratory. We measured skilled paw reaching using the "staircase test" developed by Montoya et al. [Prog. Brain Res. 82 (1990) 459], in which a rat retrieves food pellets by reaching down from a central platform to a series of descending steps on either side, grasping the pellets in its forepaw, and lifting them to its mouth. Staircase boxes were scaled for the body weights of young adult male (350 g) and female (250 g) Long-Evans rats. Studies were conducted using harmaline, a tremorigen; scopolamine; methyl scopolamine; and 2,4-dithiobiuret (DTB), a compound that causes muscle weakness by interfering with cholinergic transmission at the neuromuscular junction. Harmaline (0, 1.0, 3.0, and 10.0 mg/kg) reduced pellet retrieval only at a dose that also caused visible tremor. Both scopolamine (0, 0.1, 0.3, and 1.0 mg/kg) and methyl scopolamine (0, 0.104, 0.312, and 1.04 mg/kg) impaired pellet retrieval; scopolamine was more effective than methyl scopolamine. DTB (5 daily doses of 0, 0.1, 0.2, and 0.5 mg/kg) had no effect on retrieval, even when causing visible signs of weakness. These data cast doubt on the utility of this method for detecting and quantifying subtle chemical-induced changes in motor function in rats.

Analysis of Variance↗
PubMed2005

Enhanced secretion of tropane alkaloids in Nicotiana tabacum hairy roots expressing heterologous hyoscyamine-6beta-hydroxylase.

Hyoscyamine-6beta-hydroxylase (H6H; EC 1.14.11.11) catalyses oxidative reactions in the biosynthetic pathway leading from hyoscyamine to the more pharmaceutically valuable tropane alkaloid scopolamine. The h6h gene encoding H6H from Hyoscyamus niger was introduced, under the control of the CaMV 35S promoter, into non-hyoscyamine-producing Nicotiana tabacum and hyoscyamine-producing Hyoscyamus muticus. The transformation was performed using a binary vector system based on Agrobacterium rhizogenes. Production of scopolamine in hairy roots was clearly correlated with the 35S-h6h transcript expression. The engineered N. tabacum and H. muticus hairy roots were studied for the production of scopolamine and other tropane and nicotine alkaloids after feeding the cultures with exogenous hyoscyamine. N. tabacum hairy roots carrying the 35S-h6h transgene showed a more efficient uptake of hyoscyamine from the culture medium and a higher rate of bioconversion of hyoscyamine to scopolamine than those of H. muticus. In particular, the secretion of scopolamine in N. tabacum hairy roots was remarkably high, up to 85% of the total scopolamine being released to the culture medium. Exogenous hyoscyamine also caused changes in nicotine alkaloid accumulation in N. tabacum hairy roots.

Alkaloids↗
PubMed1998

Differential involvement of cortical receptor mechanisms in working, short-term and long-term memory.

Rats received, through bilaterally implanted indwelling cannulae, 0.5 microliter infusions of 6-cyano-7-nitroquinoxaline2,3-dione (CNQX) (0.5 microgram), D-2-amino-5-phophono pentanoic acid (AP5) (5.0 micrograms), muscimol (0.5 microgram), scopolamine (2.0 micrograms), SCH23390 (2.5 micrograms), saline or a vehicle into the CA1 region of the hippocampus, or into the antero-lateral prefrontal (PRE), posterior parietal (PP) and entorhinal cortex (EC). The infusions were given 6 min prior to one-trial step-down inhibitory avoidance training in order to measure their effect on working memory (WM), or immediately post-training in order to measure their effect on short-term (STM) and long-term memory (LTM), 1.5 and 24 h later, respectively. WM was inhibited by CNQX or muscimol given into any of the cortical areas, by SCH23390 given into CA1, PRE or PP, and by scopolamine given into PRE or EC. STM was unaffected by any of the treatments given into PRE, and was inhibited by CNQX or muscimol given into CA1, PP and EC and by scopolamine given into PP, and enhanced by SCH given into CA1. LTM was inhibited by CNQX, muscimol, scopolamine or SCH23390 given into PRE, by scopolamine given into PP, by SCH23390 given into the entorhinal cortex, and by AP5, CNQX, muscimol or scopolamine given into CA1. The results indicate a differential involvement of the various neurotransmitter systems in the three types of memory in the various brain areas, and a separation of the mechanisms and of the regions involved in each. In addition, some of the findings suggested links between WM and LTM processing in PRE, between WM and STM processing in EC and PP, and between all three types of memory in CA1.

Animals↗
PubMed1992

Cholinergic blockade and response timing in rats.

The effects of central cholinergic blockade on the temporal regulation of behaviour were studied with a two-level DRL schedule. Five-month-old male Wistar rats had to press lever A and then wait for a minimum of 5 s before pressing lever B to obtain the reinforcer (sweetened milk). After a stable baseline performance, subjects were injected in random order with the general cholinergic blocker, scopolamine, 0.15 and 0.5 mg/kg, the peripheral cholinergic blocker, methylscopolamine, 0.15 and 0.5 mg/kg, and a combination of the cholinesterase inhibitor, physostigmine, 0.2 mg/kg, and scopolamine, 0.5 mg/kg. Each drug treatment was separated by 2 days of saline treatment. Results showed that scopolamine at 0.5 mg/kg significantly impaired the temporal regulation of the A-B response sequence: the median A-B inter-response time (IRT) was shortened and the coefficient of variation of the A-B IRT distribution was increased, thus revealing a loss in the sensitivity to time. This disruption of accurate timing behaviour lowered efficiency. The drug changed neither the duration of the B-A interval nor the A-B response rate, but significantly increased the rate of the superfluous B-B sequences. Methylscopolamine was without effects and physostigmine totally or partially reversed all the scopolamine effects. These results suggest that scopolamine at 0.5 mg/kg specifically affected the mechanism(s) underlying response timing, and that the effects were not secondary to changes in activity or motivation. They partly corroborate data obtained in other procedures and support the idea that the central cholinergic system is involved in the temporal regulation of behaviour.

Animals↗
PubMed1988

Effects of anticholinergic treatment on transient behavioral suppression and physiological responses following concussive brain injury to the rat.

Increasing doses (0.1, 1.0, 10.0 mg/kg) of scopolamine were systemically (i.p.) administered to rats subjected to moderate fluid percussion brain injury. Scopolamine treatment (1.0 mg/kg, i.p.) 15 min prior to trauma significantly reduced mortality and the duration of transient behavioral suppression assessed by a variety of measures. No differences were observed between saline- and scopolamine-treated animals in either the incidence or duration of transient apnea associated with injury. Preinjury treatment with methylscopolamine (1.04 mg/kg) or mecamylamine (1.0 mg/kg) had no effect on transient behavioral suppression. Except for increased heart rate, preinjury treatment with scopolamine (1.0 mg/kg) did not significantly alter systemic physiological responses to injury. Rats treated with scopolamine (1.0 mg/kg, i.p.) 30 s after injury tended to have shorter durations of reflex and response suppression. These experiments suggest that antimuscarinics can attenuate components of transient behavioral suppression associated with concussive brain injury. These findings are consistent with previous experimental and clinical observations and lend further support to the hypothesis that activation of a muscarinic system within the CNS mediates components of reversible traumatic unconsciousness following cerebral concussion.

Animals↗
PubMed1986

Differential effects of cholinergic blockade on performance of rats in the water tank navigation task and in a radial water maze.

The disruptive effect of cholinergic blockade was tested under conditions in which either the working memory or the spatial mapping requirements of the behavioral task were emphasized. In Experiment 1, 13 rats were trained in an eight-arm radial water maze to asymptotic performance. When delays of 5, 10, 20, and 40 min were inserted between Choice 4 and Choice 5, incidence of errors in Choices 5-8 increased after pretrial (20 min) scopolamine injection (0.2 mg/kg, ip) faster than under control conditions and approached chance level with the 40-min delay. Scopolamine after Choice 4 or pretrial methylscopolamine was ineffective. In Experiment 2, 30 rats were trained in a Morris water tank. Acquisition was impaired by pretrial injection (20 min) of 0.1 and 0.2 mg/kg scopolamine, but a higher dose (1.0 mg/kg) was required to impair overtrained performance. In a working memory version of the navigation task, scopolamine administered 20 min before the first trial deteriorated retention tested 40 min later at a dose of 1.0 but not at 0.4 and 0.2 mg/kg. It is concluded that the disruptive effect of scopolamine is proportional to the demands on the working memory component of the task whereas the use of an overtrained mapping strategy is relatively resistant to cholinergic blockade.

Animals↗