Large Doses Of Atropine Research Articles

Catropin therapy of initial states of epidemic encephalitis

Chronic encephalitis, until recently, had no therapy that would give significant and lasting success. The current subject of discussion is the therapy with large doses of atropine, first tried in the Remerovsky sanatorium in Hirsau. Those conducting it speak of an improvement that can be considered practical healing (Roemer).

Study on the Mechanism of Atropine in the Treatment of Septic Shock

Atropine (atropinol) is a typical anticholinergic drug that competes for M receptors. Large doses of atropine can expand blood vessels, relieve small vasospasm, improve microcirculation as well as cardiovascular function, and inhibit thromboxane formation. It is an ideal drug for the treatment of septic shock that are worthy of clinical application. In recent years, studies have found that the main mechanisms of atropine's anti-infective shock include inhibiting calcium ion overload, improving microcirculation disorders, inhibiting thromboxane formation, reducing the release of inflammatory mediators, and inhibiting the release of glutamate. The research progress of the pharmacological effects and mechanisms of atropine in the treatment of septic shock is summarized, and it provides a basis for the in-depth study of atropine.

Organophosphate Poisoning Presenting as Acute Respiratory Distress

Sir, Organophosphate poisoning [OP] is a potentially fatal but completely treatable condition that is still very prevalent in our country. Early recognition is paramount in preventing fatality. Although rarely reported, it does occur in infants, where history may not be forthcoming and initial presentation often misleading. We report a case of aspiration pneumonia whose evolving symptomatology made us diagnose OP poisoning. A previously healthy baby presented with vomiting whilst breast feeding followed by respiratory distress and altered sensorium. No prior history of fever, respiratory illness, seizures or drug intake. On examination he was a well thriving infant, who was afebrile with severe respiratory distress. He had altered sensorium and was markedly hypotonic with small sluggishly reacting pupils. Emergency management was given and baby was intubated and ventilated. Empirical antibiotics for possible aspiration pneumonia and other supportive treatment was started. Blood counts, chest radiograph and metabolic profile were normal. In the next few hours his sensorium worsened, pupils became pin pointed and unreactive to light. Copious oropharyngeal secretions and diarrhea were also noted. This constellation of symptoms made us suspect cholinergic hyperactivity and a large dose of atropine was given, which did not produce pupil dilatation, suggesting OP poisoning [1]. To confirm cholinesterase [ChE] level [2] was done and was found to be less than 25% reference range. Atropine infusion was immediately instituted at 0.02 mg/kg/hour [5], titrated to drying of secretions. As the nature of OP compound unknown empirical dose of pralidoxime, 25 mg/kg was given to reactivate ChE enzyme [5]. In next 24 h baby showed good improvement in motor tone and power with drying of secretions, and was subsequently extubated. Retrospectively parents revealed that insecticide was sprayed around the house on that day and child most likely got exposed by inhalation. Atropine was continued for 3 days and then weaned over 24 h. Serial monitoring of ChE levels showed a steady rise in titers to normal. The baby was discharged after a week and parents were counseled on the hazards of environmental exposure to OP compounds. OP’s inhibit ChE activity and affect central and peripheral muscarinic and nicotinic receptors [2]. Unlike adults infants mainly present with acute CNS depression and are characterized by the absence of typical muscarinic effects including fasciculation and bradycardia. The pupil examination is the key [3] and pin point pupils with diarrhea at presentation, is described as a triage tool for early recognition in children [4]. As with our infant, periodic pupil examination helped clinch the diagnosis. Therapeutic trial of atropine and serum ChE levels helps to make the diagnosis, however no correlation between the level and severity is noted [2]. Treatment is aimed at decontamination, reversal of muscarinic signs with atropine and enzyme reactivation by oximes. Frequent atropine doses or as continuous infusion titrated to achieve drying of secretions is used. Single dose of pralidoxime, or in severe poisoning a continuous infusion is used. Oximes are continued for 24 h after symptoms resolve or restoration of normal serum ChE levels [5].

Complications and Carotid Stenting

Puncture site: Carotid stenting should be undertaken within an interventional (endovascular) program in which personnel are familiar with efficient and safe arterial sheath removal with minimal patient discomfort. Adequate hydration and pretreatment with atropine can prevent and treat hypotension associated with a vaso-vagal response to sheath removal. An unexplained decrease in blood pressure may be caused by retroperitoneal bleeding. Closure devices are recommended if used by trained personnel. Complications of closure devices could be disastrous (hematoma, infection, torn artery). The occurrence of spasm in the distal internal carotid artery is a common angiographic event caused by the mechanical irritation of the vessel. It usually resolves spontaneously after the catheter or guide wire has been removed. Usage of 0.014-inch softtipped wires minimizes the occurrence of spasm. Injections of 100 to 200 mg of nitroglycerine through the carotid access sheath will hasten the resolution of spasm. Spasm must be differentiated from kinking of the internal carotid artery. Bradycardia and episode of transient asystole are not uncommon during balloon inflations within the carotid bulbous. More prolonged hypotension and bradycardia were seen with balloon-expandable stents which place more sustained pressure on the baroreceptors. Both, bradycardia and asystole during balloon inflation are transient and respond promptly to balloon deflation. Prevention is pre-medication with atropine. Larger doses of atropine should be avoided in elderly patients. Hypotension is not uncommon after carotid stenting and may last from hours to days, depending on the sensitivity of the baroreceptors, the type of stent used, and whether CAS was performed bilaterally. The degree of hypotension appears to be more pronounced in heavily calcified lesions. Usually, there are no clinical sequelae and the modest decrease in blood pressure requires no specific intervention. Bed rest, sedation or narcotics exacerbate hypotension and mitigate against rapid ambulation and recovery. Patients, particularly the elderly, should be assisted with ambulation if Complications and Events Encountered During Carotid Stenting

Propofol-Nitrous Oxide Anesthesia Enhances the Heart Rate Response to Intravenous Isoproterenol Infusion

Heart rate (HR) response to IV atropine is attenuated during propofol-nitrous oxide (N2O) anesthesia. We studied the effects of propofol-N2O anesthesia on isoproterenol-induced HR changes. The control group (n = 15) received no propofol and no N2O. Patients in the propofol-N2O group (n = 21) received IV propofol 2.5 mg/kg over 1 min followed by a continuous infusion of propofol 10 mg · kg−1 · h−1. After tracheal intubation, anesthesia was maintained with propofol 5 mg · kg−1 · h−1 and 67% N2O in oxygen. All patients in both groups received IV isoproterenol at incremental infusion rates (2.5, 5, 7.5, 10, 12.5, 15, and 17.5 ng · kg−1 · min−1 for 2 min at each dose) until HR increased more than 20 bpm from baseline values. At the end of each infusion period, hemodynamic data were collected. The HR response to isoproterenol 7.5 ng · kg−1 · min−1 was increased more in the propofol group than in the control group (20 ± 5 versus 14 ± 4 bpm;P < 0.05). During the isoproterenol infusion at 10 ng · kg−1 · min−1, HR increased by more than 20 bpm in all patients in the propofol group but in only 31% of patients in the control group (P < 0.0001). These results suggest that continuous isoproterenol infusion might be useful when a large dose of atropine is ineffective in restoring normal HR during propofol-N2O anesthesia.

Heart Rate Response to Intravenous Atropine During Propofol Anesthesia

We studied the dose-response relationships for atropine-induced heart rate (HR) changes in 61 patients during propofol anesthesia. The control group (n = 15) received no propofol. Group P-5 (n = 22) received IV propofol 1.25 mg/kg over 1 min followed by propofol at 5 mg · kg−1 · h−1. After tracheal intubation, anesthesia was maintained with propofol 5 mg · kg−1 · h−1 and 67% nitrous oxide in oxygen. Group P-10 (n = 24) received IV propofol 2.5 mg/kg over 1 min followed by propofol at 10 mg · kg−1 · h−1. The P-10 protocol was otherwise identical. All patients received incremental doses of IV atropine 5 μg/kg over 5 s at 2-min intervals until HR increased >20 bpm from baseline values. Heart rate response to atropine 10 μg/kg was attenuated in Groups P-5 (12 ± 7 bpm) and P-10 (9 ± 6 bpm) compared with the control group (28 ± 13 bpm, P <0.05). When atropine 20 μg/kg was administered, HR increased >20 bpm in all patients of the control group, but in only 43% and 13% of patients in Groups P-5 and P-10, respectively (P <0.05). These results indicate the decreased HR responsiveness to IV atropine in patients receiving propofol, which cannot be effectively overcome by a large dose of atropine, is possibly attributable to propofol-induced suppression of the sympathetic nervous system.

Secretory interactions between the sympathetic and parasympathetic innervations of the submandibular gland in the anaesthetized cat.

Interactions between the sympathetic and parasympathetic innervations of the submandibular gland have been investigated in the anaesthetized cat. At low frequencies of chorda lingual (parasympathetic) stimulation, simultaneous stimulation of the ascending cervical sympathetic nerve in bursts (20 Hz for 1 s at 10 s intervals) increased the flow of submandibular saliva, but the effect was never more than additive. The output of protein was consistently reduced by simultaneous stimulation of both the sympathetic and parasympathetic innervations, below that evoked by stimulation of either alone. Sympathetic stimulation was more effective than parasympathetic stimulation in promoting the secretion of tissue kallikrein and peroxidase in the submandibular saliva. The output of the latter enzyme, in response to sympathetic stimulation, was significantly reduced by simultaneous stimulation of the parasympathetic innervation at frequencies greater than 1 Hz, but nevertheless exceeded the amount secreted during chorda stimulation alone. Thus, this protocol provided no evidence of synergy between the two divisions of the autonomic nervous system with respect to any submandibular secretory function that was recorded. However, following the administration of a small dose of atropine (2-15 micrograms kg-1 i.v.), sufficient to block secretion during chorda stimulation alone, the flow of saliva, in response to sympathetic stimulation, was potentiated when superimposed on a background of parasympathetic stimulation at all frequencies that were employed. This effect was abolished by larger doses of atropine, indicating that it was dependent upon activation of muscarinic receptors, only some of which could have been blocked by the initial dose.

Oral Clonidine Premedication Blunts the Heart Rate Response to Intravenous Atropine in Awake Children

Comment Apparently two separate groups of Japanese researchers are simultaneously investigating the premedicating potential of oral clonidine, a centrally acting α-agonist. In awake adults, oral clonidine can cause bradycardia and hypotension and reduces the chronotropic response to intravenous atropine (Nishikawa et al.). In this investigation, high-dose (4 μg/kg) oral clonidine premedication in children, 10.8 ± 1.6 yr, also attenuated the increase in heart rate (HR) produced by intravenous atropine (10 μg/ kg) but did not cause significant changes in HR or blood pressure (BP) at the same or lower (2 M-g/kg) doses. No adverse effects of atropine were reported in this study, even though atropine doses as high as 30 μg/kg were required to increase HR 20 bpm in low-dose study patients, and atropine doses of 40 μg/kg were ineffective in 2 of 16 patients in the high-dose group. In addition, premedication with high-dose oral clonidine produced significandy higher (p <0.05, test statistic unreported) sedation scores than premedication with placebo or low-dose (2 μg/kg) oral clonidine. The authors concluded that effective (4 μg/kg) premedicating doses of oral clonidine can suppress the HR response to intravenous atropine in awake children; large doses (30–40+ μg/kg) of atropine may be required to increase HR 20 bpm in children

Bronchospasm During Pneumoperitoneum

Bronchospasm During Pneumoperitoneum

Oral Clonidine Premedication Blunts the Heart Rate Response to Intravenous Atropine in Awake Children

Clonidine, which is known to have analgesic and sedative properties, has recently been shown to be an effective preanesthetic medication in children. The drug may cause side effects, including bradycardia and hypotension. This study was conducted to evaluate the ability of intravenous atropine to increase the heart rate (HR) in awake children receiving clonidine preanesthetic medication. We studied 96 otherwise healthy children, 8-13 yr old, undergoing minor surgery. They received, at random, oral clonidine 2 or 4 micrograms.kg-1 or placebo 105 min before scheduled induction of anesthesia. Part I (n = 48, 16 per group): When hemodynamic parameters after insertion of a venous catheter had been confirmed to be stable, atropine was administered in incremental doses of 2.5, 2.5, and 5 micrograms.kg-1 every 2 min. The HR and blood pressure were recorded at 1-min intervals. Part II (n = 48, 16 per group): After the recording of baseline hemodynamic values, successive doses of atropine (5 micrograms.kg-1 every 2 min, to 40 micrograms.kg-1), were administered until HR increased by 20 beats.min-1. The HR and blood pressure were recorded at 1-min intervals. Part I: The increases in HR in response to a cumulative dose of atropine 10 micrograms.kg-1 were 33 +/- 3%, 16 +/- 3%, and 8 +/- 2% (mean +/- SEM) in children receiving placebo, clonidine 2 micrograms.kg-1, and clonidine 4 micrograms.kg-1, respectively (P < 0.05). Part II: The HR in the control group increased by more than 20 beats.min-1 in response to atropine 20 micrograms.kg-1 or less. In two patients in the clonidine 4 micrograms.kg-1 group, HR did not increase by 20 beats.min-1 even after 40 micrograms.kg-1 of atropine. Oral clonidine premedication (4 micrograms.kg-1) blunted the increase in HR after intravenous atropine in awake children, although clonidine 2 micrograms.kg-1 did not. A larger dose of atropine was required to increase the HR by 20 beats.min-1 in children receiving the premedicant in the larger dose.

Effect of atropine injected into the nucleus tractus solitarius on the regulation of blood pressure

Previous experiments have demonstrated that stimulation of muscarinic cholinergi receptors in the nucleus tractus solitarius (NTS) of the rat decreases arterial blood pressure and heart rate. The present studies were designed to examine the role of cholinergic mechanisms in the NTS in the tonic regulation of arterial pressure and the baroreceptor reflex. Atropine injected into the NTS of chloralose-anesthetized rats produced a dose-dependent inhibition of cardiovascular responses elicited by injection of acetylcholine into the same site; 240 pmol atropine eliminated acetylcholine-evoked responses. Atropine also increased arterial blood pressure but only at higher doses. Even larger doses of atropine were required to alter cardiovascular responses elicited by electrical stimulation of the aortic depressor nerve. Methylatropine injected into the NTS also blocked acetylcholine-evoked responses but, in contrast to the actions of atropine, did not increase arterial pressure in the dose range required to block acetylcholine-evoked responses. Furthermore, a dose of methylatropine (1 nmol) capable of blocking acetylcholine-evoked cardiovascular responses did not alter aortic depressor nerve-evoked cardiovascular responses. This lack of an effect of methylatropine on arterial pressure and aortic depressor nerve-evoked responses was not due to limited diffusion of the drug within the NTS since 1 nmol methylatropine completely blocked acetylcholine-evoked responses even when injected 0.5 mm distant from the site of acetylcholine injection. These results suggest that cholinergic mechanisms in the NTS are not involved in the tonic regulation of cardiovascular function or the baroreceptor reflex. Furthermore, these results highlight the importance of characterizing doses of drugs used in microinjection studies.

The Influence of Atropine Dose on Recovery from Vecuronium-induced Neuromuscular Blockade

To determine whether the dose of atropine affects the rate of neostigmine-induced recovery from vecuronium-induced neuromuscular blockade, the authors monitored isometric adductor pollicis mechanical activity in 36 anesthetized (thiopental, fentanyl, nitrous oxide) adult patients (ASA physical status 1 or 2). Once surgery was completed and twitch height had spontaneously regained 25% of its initial value, the patients were randomly allocated into three groups (A10, A15, A20; n = 12 in each group) according to the dose of atropine (10, 15, or 20 micrograms/kg) that was mixed with 40 micrograms/kg neostigmine. Twitch height, train-of-four, and 50- and 100-Hz tetanic fade were recorded for 15 min after the administration of the reversal agents. No significant differences were found among the three groups in the final twitch height (95% +/- 2%), train-of-four (87% +/- 1%, 88% +/- 2%, 89% +/- 1%), and 50-Hz tetanic fade (90% +/- 1%, 94% +/- 1%, 93% +/- 1%) (mean +/- SEM). Fifteen minutes after reversal, fade in response to 100-Hz tetanus was statistically greater in the A10 group than in the two other groups (70% +/- 3% of control versus 84% +/- 4% and 81% +/- 2%) (mean +/- SEM, P less than 0.05). The present results demonstrate that larger doses of atropine facilitate neostigmine's reversal of vecuronium neuromuscular blockade. The clinical implications of the differences observed in this study remain to be determined.

Oral Clonidine Blunts the Heart Rate Response to Intravenous Atropine in Humans

Clonidine, recently introduced into anesthesia practice, may cause bradycardia. Whether this bradycardia is reversible with atropine is not known. Accordingly, we studied heart rate (HR) responses to intravenous atropine in 80 patients assigned randomly to either a control group, who received no medication (n = 20), or a clonidine group, who received oral clonidine of approximately 1.2 micrograms.kg-1 (n = 20), 2.5 micrograms.kg-1 (n = 20), or 5 micrograms.kg-1 (n = 20). All patients received incremental doses of atropine, 2.5, 2.5, and 5 micrograms.kg-1, at 2-min intervals (total dose 10 micrograms.kg-1). Positive chronotropic response to the cumulative atropine dose of 10 micrograms.kg-1 was attenuated significantly only in patients given clonidine 5 micrograms.kg-1 (7 +/- 1 beats per min, mean +/- standard error) when compared with those given smaller doses of clonidine (15 +/- 2, 16 +/- 2 beats per min) or no clonidine (19 +/- 2 beats per min) (P less than 0.05). To determine whether HR hyporesponsiveness to atropine induced by clonidine can be overcome by a larger dose of atropine, the authors studied 30 additional patients given clonidine 5 micrograms.kg-1 or no medication. In all patients not receiving clonidine (n = 15), HR increased by more than 20 beats per min when atropine of 15 micrograms.kg-1 was administered, whereas in only 5 patients (33%) receiving clonidine did the HR increase by 20 beats per min after atropine 15 micrograms.kg-1 (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacological modulation of vagal cardiac control measured by heart rate power spectrum: A possible bioequivalent probe

The autonomic cardiac control was studied as a sensitive parameter of anticholinergic treatment in humans, using heart-rate (HR) power spectrum. A cross-over placebo controlled study was performed in 8 young volunteers who received increasing bolusdoses of IV atropine (from 1.3 micrograms/kg to 29.9 micrograms/kg) or placebo. Computing the HR power spectrum and integrating over specific frequency bands, we focused in particular on the respiratory frequency band (usually between 0.2-0.4 Hz) which is purely of vagal mediation. At small atropine doses (less than 5.2 micrograms/kg), the respiratory peak increased, relative to baseline, with maximal response at 2.6 micrograms/kg (from 1.0 to 1.9 +/- 0.9). Larger doses of atropine (greater than or equal to 6.5 micrograms/kg) reduced the power of the respiratory peak, by a few orders of magnitude, in a dose-dependent way. Corresponding changes were observed in mean HR but in the opposite direction i.e., a maximal bradycardia at 2.6 micrograms/kg and a nearly two fold increase in mean HR at 29.9 micrograms/kg. We conclude that atropine has a bimodal dose-dependent effect on parasympathetic cardiac control. Since the use of HR spectral analysis has been demonstrated in various animal species, we suggest that it can be used as a sensitive noninvasive probe for animal to man transformation studies.

In vivo and in vitro studies on the use of the guinea pig as a model for virus-provoked airway hyperreactivity.

The parainfluenza 3 (P-3)-infected guinea pig was examined as a model for virus-provoked airway hyperreactivity by measuring changes in airway overflow pressure in response to intravenously (iv) administered histamine. In vitro responses of lung parenchymal strips to several contractile substances were also measured. All studies were conducted 4 days after nasal insufflation with P-3 or P-3 growth medium (control). Increases in airway overflow pressure caused by histamine were enhanced by P-3 infection, and the dose required to produce a standard level of response was decreased (i.e., there was an increase in sensitivity to histamine). Enhancement of in vivo histamine responses caused by P-3 was prevented both by cutting the vagus nerves in the midcervical region and by iv administered hexamethonium, 5 mg/kg. The enhancement was not blocked by 1 mg/kg of atropine given iv, but was blocked by a larger dose 5 mg/kg. The larger dose of atropine significantly antagonized responses to histamine in the P-3-infected state. Increases in airway overflow pressure produced by electrical stimulation of the left vagus and nicotine (1 and 10 mg/kg given iv), both studied after bilateral vagotomy and propranolol, 1 mg/kg given iv, were also enhanced by P-3 infection. Atropine, 1 mg/kg given iv blocked the P-3-induced enhancement of responses to vagus stimulation. Propranolol, 1 mg/kg, and phentolamine, 3 mg/kg, given together iv, produced a doubling of the airway overflow pressure only in P-3-infected animals. Propranolol alone or other receptor antagonists did not produce as marked a change in either group of animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Atropine: Animal models

Bradyarrhythmias, with or without hypotension, may be associated with acute myocardial infarction, especially inferior. The early use of atropine in the management of sinus bradycardia, with associated hypotension, spurred a continuing controversy that has found only partial solution in animal models. Experimentally there is increased sensory and autonomic motor activity with acute coronary occlusion. For example, in the cat, increased cholinergic activity was evidenced by the absence of bradycardia with atropinization and vagotomy, although these pretreatments accelerated the onset of significant ventricular arrhythmias. Atropine in experimentally infarcted dogs increased ischemia, while elevated heart rates reduced the threshold for ventricular fibrillation (VF) and vagal stimulation increased the threshold for VF, largely independent of heart rate. Specific clinical studies failed to support much of the animal data, although reports of tachyarrhythmias and VF resulting from the administration of atropine extended the controversy. The animal models, in the main, failed to mimic the clinical situation, for: 1) pentobarbital, with its propensity to alter some autonomic reflexes, dominated earlier work; 2) relatively large doses of atropine were employed; 3) the animals were presumed to be free of coronary and cardiac disease, factors known to influence autonomic reflexes; and 4) vagotomy and atropinization commonly preceded the acute occlusion.

Reflex responses to positive end-expiratory pressure

When positive end-expiratory pressure (PEEP) is applied to rabbits there is a large depression of cardiac output. The authors investigated the baroreceptor and lung stretch reflex responses to PEEP in rabbits to determine if reflex responses are important in causing the depression of carciac output which occurs with PEEP. With PEEP there was a depression of cardiac output and blood pressure, no change in heart rate, and an increase in systemic vascular resistance. The responses to PEEP were similar after vagotomy and after a large dose of atropine, but, after treatment with phenoxy-benzamine, blood pressure was lower during PEEP and systemic vascular resistance did not increase. The data suggests that lung stretch response is not an important factor in the cardiovascular response to PEEP in rabbits.

Some observations on the nature of neural intranuclear inclusions (Roncoroni bodies).

In experimental jejunal obstruction produced in cats, the neurones of the intermediate gray column of the cord showed bilateral intranuclear inclusions. They were also seen when hypertrophy and hyperplasia, produced in various elements of the bowel wall, were prevented by large doses of atropine. The latter observation implied that the afferent autonomic nerve supply is involved in the production of these unusual structures. The inclusion bodies were extremely rare or absent in control animals. In order to see whether these bodies occurred by chance even though they are regularly produced in the above-mentioned area, an effort was made to see whether they would appear unilaterally following stimulation of a unilateral afferent nerve. This was done by ligation and severance of the right common carotid artery below its bifurcation with or without severing its accompanying vagal trunk. Removal of the pulsatile blood supply to the carotid sinus and carotid body has long been known to produce afferent action potentials in the glossopharyngeal and vagus nerves. Within 6 h many neurones in the middle half of the ipsilateral nucleus of the tractus solitarius showed the inclusions. The cephalic end of this nucleus showed no inclusions. At the level of the obex the inclusions were present bilaterally. The inclusions also appeared in numerous other areas of the brain, brain stem and cervical cord in bilateral fashion. They were found in neurones of the neurohyphysis as well as in the cingulate gyrus. Their widespread but focal distribution corresponds to numerous areas of the cord and brain in which physiologists have produced striking effects with electric probing and stimulation. The inclusion bodies are at present conceived as representing the neuronal nuclear response to an afferent stimulus which causes an increase in the metabolic activity controlled by the nucleus.

Reserpine abolishes movement-correlated atropine-resistant neocortical low voltage fast activity

Following a large dose of atropine, rats display large amplitude slow waves in the neocortex during immobility, tremor, tooth-chattering and face-washing (Type II behavior) but display low voltage fast activity (LVFA) during walking, struggling, postural changes and head movement (Type I behavior). Rats treated with a large dose of reserpine usually continue to display LVFA during immobility as well as during movement although large amplitude slow waves are present more frequently than normal. A combination of reserpine and atropine abolishes all LVFA even during intense sensory stimulation or electrical stimulation of the reticular formation. Chlorpromazine, lysergic acid diethylamide, methysergide, phenoxybenzamine, pimozide, promethazine, propranolol and trifluoperazine do not have this effect when combined with atropine. In rats treated with nialamide prior to reserpine and atropine, LVFA continues to occur in association with Type I behavior just as in rats given atropine alone. It is proposed that the occurrence of LVFA in the neocortex is determined by two distinct reticulocortical systems. A cholinergic system produces all LVFA occurring during Type II behavior and a second system, dependent on a monoamine, produces LVFA in association with Type I behavior. The view that LVFA is a correlate of arousal or the sleep-waking cycle is criticized.

Reserpine Abolishes Movement-correlated atropine-resistant neocortical low voltage fast activity

Following a large dose of atropine, rats display large amplitude slow waves in the neocortex during immobility, tremor, tooth-chattering and face-washing (Type II behavior) but display low voltage fast activity (LVFA) during walking, struggling, postural changes and head movement (Type I behavior). Rats treated with a large dose of reserpine usually continue to display LVFA during immobility as well as during movement although large amplitude slow waves are present more frequently than normal. A combination of reserpine and atropine abolishes all LVFA even during intense sensory stimulation or electrical stimulation of the reticular formation. Chlorpromazine, lysergic acid diethylamide, methysergide, phenoxybenzamine, pimozide, promethazine, propranolol and trifluoperazine do not have this effect when combined with atropine. In rats treated with nialamide prior to reserpine and atropine, LVFA continues to occur in association with Type I behavior just as in rats given atropine alone. It is proposed that the occurrence of LVFA in the neocortex is determined by two distinct reticulocortical systems. A cholinergic system produces all LVFA occurring during Type II behavior and a second system, dependent on a monoamine, produces LVFA in association with Type I behavior. The view that LVFA is a correlation of arousal or the sleep-waking cycle is criticized.