Scopolamine Methylbromide Research Articles

Facile synthesis of Ag@Au core-satellite nanowires for highly sensitive SERS detection for tropane alkaloids

Compared with silver nanoparticles, gold nanoparticles have excellent chemical resistance and biocompatibility, while silver nanoparticles have more excellent local surface plasmon resonance characteristics than gold. In this article, we developed a simple method for growing island-shaped gold nanoparticles on the surface of silver nanowires (NWs), so that the prepared Ag@Au NWs have both the advantages of Au and Ag without their disadvantages. Furthermore, by changing the reaction parameters, we achieved the regulation of the density of island-shaped gold nanoparticles on the Ag NWs surface, thereby optimizing its LSPR performance. We use the prepared Ag@Au NWs as the base material for highly sensitive Surface enhanced Raman scattering (SERS) detection. By using 4-aminothiophenol (4-ATP) as the test molecule to explore the uniformity of the prepared SERS substrate, the detection limit of 4-ATP reached 10-9 M. And 10 points were randomly selected for testing and the RSD was 7.4%, indicating the Ag@Au NWs SERS substrates had excellent uniformity. Furthermore, we have achieved highly sensitive SERS detection of 5 tropane alkaloids including L-Hyoscyamine, Anisodamine, Scopolamine Hydrobromide, scopolamine methyl bromide and scopolamine butyrate bromide. The limit of detection is 10-9 M, 10-10 M, 10-9 M, 10-9 M and 10-10 M. Furthermore, by analyzing the obtained SERS spectra, we realized the differentiation of 5 kinds of tropane alkaloids by their characteristic peaks.

Local and generalized sensitization of thermally evoked defensive behavior in caterpillars.

In addition to camouflage and chemical toxicity, many caterpillars defend themselves against predators with sudden sharp movements. For smaller species, these movements propel the body away from the threat, but in larger caterpillars, such as the tobacco hornworm, Manduca sexta, the movement is a defensive strike targeted to a noxious stimulus on the abdomen. Previously, strikes have been studied using mechanical stimulation like poking or pinching the insect, but such stimuli are hard to control. They also introduce mechanical perturbations that interfere with measurements of the behavior. We have now established that strike behavior can be evoked using infra-red lasers to provide a highly localized and repeatable heat stimulus. The latency from the end of an effective stimulus to the start of head movement decreased with repeated stimuli and this effect generalized to other stimulus locations indicating a centrally mediated component of sensitization. The tendency to strike increased with two successive subthreshold stimuli. When delivered to different locations or to a single site, this split-pulse stimulation revealed an additional site-specific sensitization that has not previously been described in Manduca. Previous work shows that strong stimuli increases the effectiveness of sensory stimulation by activating a long-lasting muscarinic cation current in motoneurons. Injection of muscarinic cholinergic antagonists, scopolamine methyl bromide or quinuclidinyl benzilate, only decreased the strike probability evoked by paired stimuli at two locations and not at a single site. This strongly suggests a role of muscarinic acetylcholine receptors in the generalized sensitization of nociceptive responses in caterpillars.

The effect of scopolamine on matching behavior and the estimation of relative reward magnitude.

We investigated the behavioral effects of scopolamine on rats that bar pressed for trains of electrically stimulating pulses under concurrent variable interval schedules of reward. For the first half of the session (30 min) a 1:4 ratio in the programmed number of stimulation trains delivered at each option was in effect. At the start of the second half of the session, an unsignaled reversal in the relative train number (4:1) occurred. We tracked the relative magnitude of reward estimated for each contiguous pair of reinforced visits to competing options. Scopolamine hydrobromide led to a reduction in the relative magnitude of reward. A similar result was obtained in a follow-up test in which relative magnitude was manipulated by varying the pulse frequency of stimulation, while equating the train number at each option. The effect of scopolamine hydrobromide could not be attributed to undermatching, side bias, nor to an effect of scopolamine on the reward integration process. When the same rats were treated with scopolamine methylbromide, no effects on matching behavior were observed. Our results suggest a cholinergic basis for the computation of choice variables related to matching behavior. (PsycINFO Database Record

Cyclooxygenase-2 identified as a potential target for novel radiomodulator scopolamine methyl bromide: An in silico study

Abstract Background The lack of a safe and effective drug against radiation injury is a major hurdle in management of these diseases. Owing to unprecedented radionuclear threats and accidents that may occur, screening of Johns Hopkins Clinical Compound Library (JHCCL) was carried out in zebrafish embryos for identifying novel radio modulators against lethal radiation injury and death. This repositioning strategy with the Food and Drug Administration (FDA) approved small molecules identified scopolamine methyl bromide (SMB) as a novel radioprotective and mitigative agent against 20 Gy gamma irradiation dose. The present study is an attempt to identify the potential target of SMB, which may also prove beneficial as a therapeutic target for other SMB like molecules in ameliorating radiation induced injury and death. Method We have performed in silico studies with structural similarity search tool, using Tanimoto coefficient (Tc) index for identification of a molecule amongst known radioprotectors that acts as the lead reference compound and helps predict SMB activity. A similar analysis with JHCCL was done to predict and identify more SMB like molecules that may contribute to radiomodulation in a similar manner. Further, molecular docking was performed on computational AutoDock Vina platform to predict the novel target for SMB, with identified lead from the known radiomodulators (RM) as the reference compound. DUD-E decoys were used as benchmark for validating our virtual studies. Results A structural analysis of SMB with JHCCL and collection of known radioprotectors has revealed its close resemblance to atropine, a known radioprotector. It exhibited Tc index of 0.66. Four more structural entities were found from JHCCL bearing close structural resemblance to SMB and atropine. Molecular docking studies performed with muscarinic receptor M2 (reported target of atropine) exhibited similar binding energies (BEs) for atropine and SMB (−9.4 and −9.7 kcal/mol respectively), and a three-dimensional superimposed binding conformation of SMB and atropine. Due to known activity of atropine as an anti-inflammatory agent and as Cyclooxygenase-2 (Cox-2) antagonist, SMB when evaluated for antagonism against Cox-2 receptor exhibited novel inhibitory action. SMB exhibited BE similar to indomethacin (chosen as the reference lead), an established radioprotector due to its potent Cox-2 inhibitory activity. Molecular docking studies revealed similar binding conformation of SMB and indomethacin with BE of −8.0 and −8.2 kcal/mol respectively. DUD-E study further validated SMB to behave as an active ligand for antagonizing Cox-2 in comparison to the decoys. Conclusion These results emphasised that SMB could be a potent non-steroidal anti-inflammatory agent contributing towards radioprotection/mitigation by inhibiting Cox-2.

Ferulic acid reverses the cognitive dysfunction caused by amyloid β peptide 1-40 through anti-oxidant activity and cholinergic activation in rats.

Cholinergic dysfunction and oxidation stress are the dominant mechanisms of memory deficit in Alzheimer's disease (AD). This study describes how ferulic acid (FA) ameliorates cognitive deficits induced by mecamylamine (MECA), scopolamine (SCOP), central acetylcholinergic neurotoxin ethylcholine mustard aziridinium ion (AF64A) and amyloid β peptide (Aβ1-40). This study also elucidates the role of anti-oxidant enzymes and cholinergic marker acetylcholinesterase (AChE) in the reversal of FA from Aβ1-40-induced cognitive deficits in rats. At 100 mg/kg, FA attenuated impairment induced by MECA and SCOP plus MECA; however, this improvement was not blocked by the peripheral muscarinic receptor antagonist scopolamine methylbromide (M-SCOP). At 100 and 300 mg/kg, FA also attenuated the impairment of inhibitory passive avoidance induced by AF64A. Further, FA attenuated the performance impairment and memory deficit induced by Aβ1-40 in rats, as did vitamin E/C. FA reversed the deterioration of superoxide dismutase (SOD) and AChE activities, and the glutathione disulfide (GSSG) and glutathione (GSH) levels in the cortex and hippocampus. Vitamin E/C only selectively reversed deterioration in the hippocampus. We suggest that FA reduced the progression of cognitive deficits by activating central muscarinic and nicotinic receptors and anti-oxidant enzymes.

Effect of perampanel, a novel AMPA antagonist, on benzodiazepine-resistant status epilepticus in a lithium-pilocarpine rat model.

This study assessed the efficacy of diazepam, and the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor antagonists perampanel and GYKI52466 in a lithium-pilocarpine status epilepticus (SE) model. SE was induced in rats using lithium chloride, scopolamine methyl bromide, and pilocarpine. Diazepam 10, 20, or 40 mg kg−1, or perampanel 1, 2.5, 5, or 8 mg kg−1 were administered intravenously at 10 or 30 min after seizure onset, and GYKI52466 50 mg kg−1, or combinations of diazepam 2.5–5 mg kg−1 and perampanel 0.5–1 mg kg−1, were administered intravenously at 30 min after seizure onset. Diazepam 20 mg kg−1 terminated seizures (based on electroencephalography and assessment of behavioral seizures) in 2/6 rats at 10 min and 0/6 rats at 30 min (ED50: 10 min, 30 mg kg−1; 30 min, not determined). Perampanel 8 mg kg−1 terminated seizures in 6/6 rats at both 10 and 30 min (ED50: 10 min 1.7 mg kg−1; 30 min, 5.1 mg kg−1). GYKI52466 50 mg kg−1 terminated seizures in 2/4 rats at 30 min. Co-administration of diazepam 5 mg kg−1 and perampanel 1 mg kg−1 terminated seizures in 9/9 rats at 30 min. In conclusion, perampanel and GYKI52466 provided efficacy in a lithium-pilocarpine SE model at 30 min after seizure onset, when SE was refractory to diazepam, supporting the therapeutic potential of AMPA receptor antagonists for refractory SE. The perampanel dose required to terminate seizures was reduced by combination with diazepam, suggesting synergy.

β-Hydroxybutyrate increases the pilocarpine-induced seizure threshold in young mice

This study was designed to investigate the effects of β-hydroxybutyrate (BHB) on pilocarpine-induced seizures in young mice. Eighty-five male, postnatal day 21, ICR mice were used. All mice were pretreated with scopolamine methylbromide (1mg/kg) 30min prior to pilocarpine administration. Experimental mice (n=46) were injected intraperitoneally with BHB (20mmol/kg), 15min prior to pilocarpine administration; control animals (n=39) were administered normal saline. Pilocarpine (300mg/kg) was then administered intraperitoneally to induce seizures. Mice were monitored for 2h after pilocarpine injection, and seizure behavior grades were evaluated according to Racine’s scale. All mice developed typical seizure behaviors of grade 3 or higher. Although the severity in terms of seizure behavior grade was not significantly different between groups, the mean (±SD) latency to the onset of seizure was significantly prolonged in BHB-treated mice (5.15±2.19min) compared with controls (2.95±1.06min; p<0.001). This study demonstrates that treatment with BHB significantly prolongs the latency to the onset of seizures induced by pilocarpine in mice and suggests that BHB, one of the ketone bodies, may be direct anticonvulsant.

Nucleus accumbens acetylcholine and food intake: Decreased muscarinic tone reduces feeding but not food-seeking

Separate groups of food-deprived rats were given 2 h access to food after receiving bilateral nucleus accumbens infusions of the muscarinic antagonist scopolamine methyl bromide (at 0, 1.0, and 10.0 μg/side), the M2-preferring agonist oxotremorine sesquifumarate (Oxo-S; at 0, 1.0, or 10.0 μg/side) or the M2 antagonist AFDX-116 (at 0, 0.2, or 1.0 μg/side). Injections of scopolamine or Oxo-S, but not AFDX-116, reduced food consumption across the 2 h. These experiments confirm a critical role for Acb acetylcholine in promoting food ingestion, and suggest that decreased acetylcholine tone at post-synaptic muscarinic receptors disrupts normal consummatory behavior.

Petroleum ether extract of Cnidium monnieri ameliorated scopolamine-induced amnesia through adrenal gland-mediated mechanism in male rats

Aim Our previous study indicated petroleum ether layer of Cnidium monnieri L. Cuss. (CM) and its ingredient osthole could alleviate scopolamine-induced amnesia in female rats. Materials and methods Hence, this study was desired to investigate the mechanism of the ameliorating effects of petroleum ether layer of CM on the performance impairment of inhibitory avoidance task and Morris water maze induced by scopolamine in male rats. Results CM at 0.1–0.6 g/kg orally administered 60 min before the training trial ameliorated the scopolamine-induced performance impairment on inhibitory avoidance learning and water maze in male rats. Only adrenalectomy but not peripheral cholinergic antagonist scopolamine methylbromide and catecholaminergic neurotoxin 6-hydroxydopamine blocked the ameliorating effects of CM on scopolamine-induced performance impairment in rats. Conclusion Therefore, we demonstrated that the ameliorating effects of CM on scopolamine-induced performance impairment may be related to activating the adrenal gland and central acetylcholingeric neuron, instead of peripheral nervous system.

Hemodynamic consequences of chronic parasympathetic blockade with a peripheral muscarinic antagonist

Whereas the sympathetic nervous system has a well-established role in blood pressure (BP) regulation, it is not clear whether long-term levels of BP are affected by parasympathetic function or dysfunction. We tested the hypothesis that chronic blockade of the parasympathetic nervous system has sustained effects on BP, heart rate (HR), and BP variability (BPV). Sprague-Dawley rats were instrumented for monitoring of BP 22-h per day by telemetry and housed in metabolic cages. After the rats healed from surgery and a baseline control period, scopolamine methyl bromide (SMB), a peripheral muscarinic antagonist, was infused intravenously for 12 days. This was followed by a 10-day recovery period. SMB induced a rapid increase in mean BP from 98 +/- 2 mmHg to a peak value of 108 +/- 2 mmHg on day 2 of the SMB infusion and then stabilized at a plateau value of +3 +/- 1 mmHg above control (P < 0.05). After cessation of the infusion, the mean BP fell by 6 +/- 1 mmHg. There was an immediate elevation in HR that remained significantly above control on the last day of SMB infusion. SMB also induced a decrease in short-term (within 30-min periods) HR variability and an increase in both short-term and long-term (between 30-min periods) BPV. The data suggest that chronic peripheral muscarinic blockade leads to modest, but sustained, increases in BP, HR, and BPV, which are known risk factors for cardiovascular morbidity.

The ameliorating effects of LiuWei Dihuang Wang on cycloheximide-induced impairment of passive avoidance performance in rats

The ameliorating effects of aqueous and ethanolic extracts of LiuWei Dihuang Wang (LDW W and LDW E) after single, 1-week or 2-week consecutive treatment on the cycloheximide-induced amnesia by using the passive avoidance task in rats were studied. After single treatment, LDW W and LDW E (1 and 2 g/kg) significantly prolonged the shortened step-through latency induced by CXM and their potency was equal. LDW W at 1 g/kg after 1-week consecutive treatment or at 0.1 g/kg after 2-week consecutive treatment almost completely reversed CXM-induced amnesia. LDW W at any dose alone after single, 1-week or 2-week consecutive treatment did not influence the step-through latency in the training trial in rats. Furthermore, muscarinic antagonist scopolamine, peripheral cholinergic antagonist scopolamine methylbromide, serotonin precursor 5-hydroxytryptamine and serotonin releaser p-chloroamphetamine could block the ameliorating effects of LDW W. GABA A receptor antagonist bicuculline and GABA B receptor agonist baclofen also blocked the ameliorating effects of LDW W. These results suggest that the ameliorating effects of LDW whose potency were parallel to treatment duration might be related to activating peripheral cholinergic neuronal system and modulating the central nervous system.

Muscarinic receptor antagonism of the nucleus accumbens core causes avoidance to flavor and spatial cues.

Pharmacological blockade of muscarinic receptors in the nucleus accumbens reduces food intake and instrumental behaviors that are reinforced by food delivery. Nucleus accumbens muscarinic antagonism may specifically suppress the hedonic or reinforcing effects of food, thus blocking its capacity to direct behavior. Alternatively, muscarinic receptor blockade may cause a negative hedonic state that interferes with appetitive learning and food intake. In these experiments, rats received infusions of scopolamine methyl bromide (10 microg/0.5 microl) into the nucleus accumbens core, following exposure to a novel flavor of liquid diet (Experiment 1) or prior to being placed into a place preference apparatus (Experiment 2). In both experiments, nucleus accumbens muscarinic receptor antagonism caused subsequent avoidance of the paired cue (flavor or spatial location). This effect was specific to cholinergic manipulation; no conditioned taste avoidance was observed after pairing the novel flavor with nucleus accumbens core antagonism of N-methyl-D-aspartate, dopamine D-sub-1, or opioid receptors (Experiment 3). These experiments confirm previous reports of a critical role for striatal acetylcholine in modulating goal-directed behaviors, but suggest caution when interpreting behavioral effects of pharmacological manipulation of striatal acetylcholine.

Blood–brain barrier and electromagnetic fields: Effects of scopolamine methylbromide on working memory after whole-body exposure to 2.45 GHz microwaves in rats

We first verified that our 12-arm radial maze test enabled demonstration of memory deficits in rats treated with the muscarinic antagonist scopolamine hydrobromide (0.5 mg/kg, i.p.). We then investigated whether a systemically-injected quaternary-ammonium derivate of this antagonist (scopolamine methylbromide; MBR), which poorly crosses the blood–brain barrier (BBB), altered maze performance after a 45-min exposure to 2.45 GHz electromagnetic field (EMF; 2 μs pulse width, 500 pps, whole-body specific energy absorption rate [SAR] of 2.0 W/kg, ±2 dB and brain averaged SAR of 3.0 W/kg, ±3 dB); if observed, such an alteration would reflect changes in BBB permeability. The drug was injected before or after exposure. Controls were naïve rats (no experience of the exposure device) and sham-exposed rats (experience of the exposure device without microwaves). In a final approach, rats were subjected to i.v. injections of Evans blue, a dye binding serum albumin, before or after EMF exposure. Whether scopolamine MBR was injected before or after exposure, the exposed rats did not perform differently from their naïve or sham-exposed counterparts. Thus, EMFs most probably failed to disrupt the BBB. This conclusion was further supported by the absence of Evans blue extravasation into the brain parenchyma of our exposed rats.

A Chronic Implant to Record Electroretinogram, Visual Evoked Potentials and Oscillatory Potentials in Awake, Freely Moving Rats for Pharmacological Studies

Electroretinogram (ERG), widely used to study the pharmacological effects of drugs in animal models (e.g., diabetic retinopathy), is usually recorded in anesthetized rats. We report here a novel simple method to obtain chronic implantation of electrodes for simultaneous recording at the retinal and cortical levels in freely moving, unanesthetized animals. We recorded cortical (VEPs) and retinal (ERGs) responses evoked by light (flash) stimuli in awake rats and compared the results in the same rats anesthetized with urethane (0.6 mg/kg) before and after the monocular administration of scopolamine methyl bromide (1‰solution). We also compared the retinal responses with those derived from a classic acute corneal electrode. Anesthesia induced consistent changes of several VEP and ERG parameters like an increase of both latency and amplitude. In particular, the analysis of the variation of latency, amplitude, and spectral content of rapid oscillatory potentials could be important for a functional evaluation of the visual system in unanesthetized versus anesthetized animals.

Effects of low‐dose scopolamine on locomotor activity: No dissociation between cognitive and non‐effects

AbstractAttempts have been made to dissociate the cognitive effects of scopolamine from its non‐cognitive effects. It has been suggested that low doses of scopolamine may induce memory impairment without inducing significant non‐cognitive effects. We therefore tested changes in locomotor activity (as a non‐cognitive effect) in rats treated with low‐dose scopolamine (which is believed to induce cognitive effects only).In this study, locomotor activity (as a non‐cognitive effect) induced by low doses of this drug was evaluated by using two methods and rat strains. In the first study (circular box method, an automated open‐field), scopolamine hydrobromide (HBr), scopolamine methylbromide (MeBr) or saline was injected subcutaneously into male Sprague‐Dawley rats. After 30 min, rats were put into an automated open‐field and locomotor activity was quantified by recording interruptions of infrared beams, with print‐outs every 2 min for 16 min. Locomotor activity was assessed by summing these recordings. In the second study (closed platform), scopolamine HBr or saline was injected intraperitoneally into male Long‐Evans rats. Twenty minutes later, the rats were placed in the center of a square‐shaped closed platform (with 3×3 divisions). Locomotor activity was defined as the sum of crossings (traversing of four paws of the rat from one area into another of nine) and rears, which were recorded every 5 min for 20 min.Results from the circular box study showed that scopolamine HBr produced a marked increase in locomotor activity whereas scopolamine MeBr produced a non‐significant decrease in locomotor activity. The closed platform data also demonstrated that scopolamine HBr increased locomotor activity significantly.These data show that scopolamine can induce non‐cognitive effects (such as increased locomotor activity), even at low doses. Our results also imply that the increase in locomotor activity is mediated centrally.

Comparative effects of scopolamine and quinpirole on the striatal fos expression induced by stimulation of D 1 dopamine receptors in the rat

Treatment of intact rats with the full D 1 dopamine agonist A-77636 induced Fos-like immunoreactivity in the medial and, to a lesser extent, the lateral portions of the striatum. Pretreatment with the muscarinic antagonist scopolamine hydrobromide (1.5–6 mg/kg) potentiated the response to A-77636 and eliminated the mediolateral staining gradient seen after A-77636 alone. Similar effects were not produced by scopolamine methylbromide, which fails to cross the blood–brain barrier, demonstrating that the actions of scopolamine were centrally mediated. The effects of scopolamine were further compared to those of the D 2-like dopamine agonist quinpirole using a factorial design in which subjects were pretreated with either scopolamine, quinpirole, or a combination of the two drugs before receiving A-77636. Pretreatment with either scopolamine or quinpirole increased staining in the lateral striatum, but the combination of the two drugs was no more effective than was quinpirole alone. Pretreatment with quinpirole, but not scopolamine, resulted in a markedly ‘patchy’ pattern of staining and actually suppressed staining in the region between patches in the medial striatum. These findings demonstrate that there are both differences and similarities between the effects of scopolamine and quinpirole on D 1 agonist-induced Fos expression and suggest that although inhibition of cholinergic neurons may be one of the mechanisms through which the effects of quinpirole are produced, other factors must also contribute.

Reversal caused by n-butylidenephthalide from the deficits of inhibitory avoidance performance in rats.

The present study was designed to investigate the mechanism of action of n-butylidenephthalide on the deficits of inhibitory avoidance performance induced by drugs in rats with piracetam as a positive control. n-Butylidenephthalide attenuated the scopolamine-induced and mecamylamine-induced acquisition impairment, and also attenuated the acquisition impairment induced by scopolamine plus mecamylamine. Furthermore, scopolamine methylbromide, a peripheral cholinergic muscarinic receptor antagonist, did not block the counteracting effect of n-butylidenephthalide on the scopolamine-induced acquisition impairment. n-Butylidenephthalide attenuated the impairment of inhibitory avoidance performance induced by the central acetylcholinergic neurotoxin AF64A administered intracisternally. From the above results, we suggest that n-butylidenephthalide attenuated the deficits of inhibitory avoidance performance induced by drugs, which are the effects related to activating the central but not the peripheral cholinergic neuronal system via muscarinic and nicotinic receptors.

Central muscarinic inhibition of lower urinary tract nociception

Previous studies indicate cholinergic systems suppress somatic nociception. The present studies determined if cholinergic muscarinic systems suppress visceral nociception, specifically, chemical irritation of the lower urinary tract. Bladders of urethane-anesthetized rats were cannulated through the dome for continuous-infusion cystometrogram recordings. EMG electrodes recorded anal sphincter activity. Infusion of 0.5% acetic acid into the bladder to produce irritation increased bladder activity and anal sphincter activity (i.e. activation of a nociceptive vesicoanal reflex). Oxotremorine (a muscarinic agonist) and (−)butylthio[2.2.2] (a mixed muscarinic agonist/antagonist) dose-dependently inhibited vesicoanal reflex activity. This inhibition was antagonized by atropine (a centrally active muscarinic antagonist) but not by scopolamine methylbromide (a peripherally restricted muscarinic antagonist). Physostigmine (a centrally active cholinesterase inhibitor) also dose-dependently inhibited vesicoanal reflex activity in an atropine-sensitive manner, while neostigmine (a peripherally restricted cholinesterase inhibitor) did not. Atropine alone (i.e. administered without prior administration of muscarinic agonist or cholinesterase inhibitor) produced robust but transient (15 min) increases in vesicoanal activity and bladder activity under conditions of acetic acid infusion into the bladder. Under conditions of saline infusion into the bladder, atropine had the opposite effect on bladder activity (i.e. inhibition). These studies indicate that an endogenous cholinergic muscarinic system can be activated by lower urinary tract irritation to suppress visceral nociception through central nervous system mechanisms.

Effects of scopolamine on a novel choice serial reaction time task

Rats were trained on a novel attentional task adapted from the five-choice serial reaction time test first developed by Carli et al. [1983; Behav. Brain. Res., 9, 361-80]. The novel task required rats to detect the occurrence of brief light flashes in one of two spatial locations following trial initiation by a lever press. Blank trials were interleaved with stimulus trials and the rat had to make a different response to indicate the absence of a light. Occasional light-alone trials were also presented in which the visual stimulus appeared without forewarning. Pre-exposure to food for 60 min prior to test increased response omissions for all trials and slowed correct response latency, but failed to significantly alter accuracy. A decrease in light-stimulus duration (1-0.4 s) decreased accuracy, increased the reporting of blank trials and the number of light-alone trial omissions. Scopolamine (0.03-0.1 mg/kg) and scopolamine methylbromide (0.1 mg/kg) failed to affect accuracy, but increased light-alone trial omissions and lengthened correct response latency. The results confirm that the novel task is able to distinguish between motivational and attentional manipulations, and imply that scopolamine affected performance via nonattentional mechanisms.

Scopolamine disruption of behavioral and hippocampal responses in appetitive trace classical conditioning

Twelve young rabbits (3–6 months; Oryctolagus cuniculus) were classically conditioned in a trace jaw movement paradigm (300 ms tone, 450 ms trace, 200 ms intraoral water) after implantation of electrodes into area CA1 of dorsal hippocampus. Rabbits were divided into two groups and administered either 0.5 mg/kg scopolamine hydrobromide (HBr) or 0.5 mg/kg scopolamine methylbromide (MBr) subcutaneously before daily training sessions. Rabbits given HBr took significantly more trials to reach a behavioral criterion of eight conditioned responses in any nine consecutive trials than rabbits given MBr ( P=0.03). Conditioned, but not unconditioned, rhythmic jaw movement responses of the HBr group were of a lower frequency (Hz) than those of MBr rabbits ( P=0.02). The magnitude of hippocampal conditioning-related responses across the first 3 days of training was significantly smaller for HBr rabbits than for MBr rabbits ( P=0.02). These effects of central cholinergic blockade are similar to those reported for undrugged aging rabbits trained in the same paradigm (Seager MA, Borgnis RL, Berry SD. Neurobiol. Aging 1997;18(6):631–639).