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Analysis of some central actions of nicotine injected into the cerebral ventricles of cats.

1. In unanaesthetized cats intraventricular injections of 2.5-10 mug nicotine produced blinking, narrowing of the palpebral fissures, retching, vomiting and asynchronous twitching of the ears. With larger doses (30-100 mug) the ear twitching was interrupted for a short time by laying back of the ears. Respiration first became laboured and deep, then rapid and shallow following which panting occurred. There was salivation, loud calling, micturition and defaecation. With still larger doses (300-1000 mug) there was torticollis, ataxia and blind charging sometimes followed by a clonic-tonic convulsion.2. In cats anaesthetized with chloralose only some of these effects followed the intraventricular injection of nicotine, i.e. the ear response, respiratory changes and salivation. In addition, the pinna reflex was facilitated.3. The ear response and the facilitation of the pinna reflex did not occur on perfusion of nicotine from a lateral ventricle to aqueduct. They result from an action on superficial structures in the cervical cord between C1 and C2. Applied to this region of the cord, nicotine produced the ear response within 10-60 sec, sometimes in concentrations as low as 1/100,000. Applied below C2, nicotine was ineffective.4. Transecting the cord below C2 or cutting the dorsal and ventral roots of C1, C2 and C3 bilaterally did not affect the ear response produced by topical application or by intraventricular injection of nicotine. Transection of the cord above C1 abolished it.5. Hexamethonium applied to the cervical cord between C1 and C2 inhibited the ear response and the facilitation of the pinna reflex whether produced by nicotine applied topically or injected intraventricularly.6. The salivation and the respiratory changes produced by intraventricular injections of nicotine did not occur when nicotine was perfused from a lateral ventricle to the aqueduct. They result from an action of the nicotine on structures situated superficially in the brain stem. Nicotine had no sialogogue or respiratory effect when applied to the region of the cord at which it produced an ear response, but perfused through the subarachnoid space from interpeduncular fossa to cisterna magna or injected into the subarachnoid space alongside the brain stem, it produced these effects.7. Hexamethonium perfused from interpeduncular fossa to cisterna magna inhibited the salivary secretion as well as the respiratory changes produced by nicotine similarly applied.8. The efferent pathway for the salivation is parasympathetic since it no longer occurred after cutting the chorda-lingual nerve or after intravenous atropine.9. Intravenous injections of nicotine also produced the ear response with facilitation of the pinna reflex, salivation and hyperventilation in the anaesthetized cat, but only the ear response and facilitation of the pinna reflex are central effects. The salivation and hyperventilation following intravenous injection are due to peripheral actions of nicotine.

Journal Article↗

[Symptoms of rabies in pets and domestic animals in South Africa and South West Africa (author's transl)].

The most obvious symptoms of rabies in farm animals and pets in South Africa and South-West Africa are discussed in the light of information obtained during routine examination of specimens for the 10-year-period 1967--1976. More than 55% of the cases encountered were cattle in which the most obvious symptoms were salivation (92%), bellowing (69%), aggressiveness (47%), paresis or paralysis (30%) and straining (12%). Unlike cattle, the most obvious symptom in goats was aggressiveness (83%). Salivation was observed in ony 29% of goats but, like bellowing in cattle, bleating was very obvious in 72% of cases. Sheep were usually quiet, but 67% were aggressive. Salivation was observed in 30%, while 27% showed an abnormal sexual desire. The second highest incidence of rabies was recorded in dogs (20%). Aggressiveness was the most obvious symptom (71%) followed by salivation (48%), paresis and paralysis (28%) and barking (11%). With the exception of salivation and paresis, which were rarely encountered, aggressiveness was the only symptom observed in cats. Several cats were encountered with rabies-like symptoms due to organic phosphate poisoning. The most obvious symptoms in horses and donkeys were aggressiveness (77%), paresis or paralysis 33%), the chewing of foreign matter (33%) and salivation 22%). It is obvious that other conditions can easily be confused with rabies. Therefore every possible cause for rabies-like behaviour must be considered and eliminated to avoid unnecessary destruction of animals.

Animals↗

Enhanced sensitivity to naltrexone is associated with an up-regulation in GABA receptor function.

Rats were made sensitive to the effects of the opioid antagonist naltrexone by treating them once weekly with cumulative doses of the drug (1, 3, 10, 30 and 100 mg/kg). Sensitization was monitored by measuring salivation following naltrexone administration. During the first week of treatment, no salivation was noted following any dose of naltrexone. Over a period of 8 weeks, however, increasing amounts of salivation were noted, with the most salivation occurring at the higher doses. Animals treated for 8 weeks with saline never salivated following injections. Following the development of sensitivity to naltrexone, the rats were sacrificed and their brains were assayed for GABA receptor function. GABA-stimulated chloride uptake, a measure of GABA receptor function, was unchanged in the cortex, but was increased in the cerebellum. These results suggest that the effects of naltrexone on cerebellar GABA receptors may be involved in the development of enhanced sensitivity to opioid antagonists.

Animals↗

Atrial natriuretic factor modifies the composition of induced-salivary secretion in the rat.

We have previously reported that although the atrial natriuretic factor (ANF) was not a sialogogic agonist, it enhanced cholinergic, alpha-adrenergic and peptidergic (substance P) stimulated salivation in the submaxillary and parotid gland of the rat. The purpose of the present work was to study whether ANF modified the composition of agonist-induced saliva in the rat. Results showed that in the submaxillary gland, ANF increased sodium and decreased potassium excretion when salivation was stimulated by methacholine (MC) or substance P (SP). However, when salivation was induced by methoxamine (MX), ANF only increased sodium excretion. On the other hand, in the parotid gland, ANF increased both sodium and potassium excretion when salivation was induced either by MC or SP but did not modify electrolyte output in MX induced salivary secretion. Protein output and amylase activity were not modified by the presence of ANF when the aforementioned sialogogic agonists were used to elicit salivation in either gland. Although ANF did not modify the volume of isoproterenol (IP) induced saliva, it increased protein output in both glands and it increased amylase activity in the parotid gland. The present results suggest that ANF may play a role in the modulation of salivary secretion in the parotid and submaxillary glands of the rat. ANF effect is likely to be mediated by modifications in the calcium level linked to phosphoinositide metabolism within the acinar and/or the ductal cells of the salivary glands.

Animals↗

The role of cognitive factors in cue reactivity: extinction on demand.

Cue reactivity measures have become common in addictions research for their apparent objectivity. We used an analog paradigm to examine whether such measures are subject to impression management. Students with conditioned reactions of salivation to the sight and smell of a lemon were assigned to a control group, an experimental group asked to reduce salivation, or an experimental group asked to reduce salivation and promised a reward if successful. Both experimental groups reduced salivation more than the control group; the group rewarded for reduction reduced salivation more than the group that was only asked to do so. This suggests that cue reactivity measures can be manipulated by research participants or clients in treatment. Suggestions for research and implications for treatment are addressed.

Analysis of Variance↗

In vivo antimuscarinic actions of the third generation antihistaminergic agent, desloratadine.

BACKGROUND: Muscarinic receptor mediated adverse effects, such as sedation and xerostomia, significantly hinder the therapeutic usefulness of first generation antihistamines. Therefore, second and third generation antihistamines which effectively antagonize the H1 receptor without significant affinity for muscarinic receptors have been developed. However, both in vitro and in vivo experimentation indicates that the third generation antihistamine, desloratadine, antagonizes muscarinic receptors. To fully examine the in vivo antimuscarinic efficacy of desloratadine, two murine and two rat models were utilized. The murine models sought to determine the efficacy of desloratadine to antagonize muscarinic agonist induced salivation, lacrimation, and tremor. Desloratadine's effect on the cardiovascular system was explored in both rodent models. RESULTS: In the pithed rat, both desloratadine (1.0 mg/kg, i.v.) and the muscarinic M2 selective antagonist, methoctramine (0.5 mg/kg, i.v.), inhibited negative inotropic (left ventricular dP/dt) effects caused by oxotremorine, a nonselective muscarinic agonist (p < 0.05). Negative chronotropic effects caused by oxotremorine were inhibited by desloratadine, methoctramine, and the muscarinic M3 selective antagonist, 4-DAMP (1.0 mg/kg, i.v.). A late positive inotropic event observed after the initial decrease was inhibited by all three test compounds with desloratadine and 4-DAMP being the most efficacious. In the conscious animal, inhibition of baroreflex-mediated bradycardia was evaluated. Unlike atropine (0.5 mg/kg, i.v.), desloratadine did not alter this bradycardia. The antimuscarinic action of desloratadine on salivation, lacrimation, and tremor was also explored. In urethane-anesthetized (1.5 g/kg, i.p.) male ICR mice (25-35 g) desloratadine (1.0, 5.0 mg/kg) did not inhibit oxotremorine-induced (0.5 mg/kg, s.c.) salivation, unlike atropine (0.5 mg/kg) and 4-DAMP (1.0 mg/kg). In conscious mice, desloratadine failed to inhibit oxotremorine-induced (0.5 mg/kg, s.c.) salivation, lacrimation, and tremor. However, desloratadine did inhibit oxotremorine-induced tremor in phenylephrine pretreated animals. CONCLUSION: The presented data demonstrate that the third generation antihistamine, desloratadine, does not significantly antagonize peripheral muscarinic receptors mediating salivation and lacrimation, therefore, xerostomia and dry eyes should not be observed with therapeutic use of desloratadine. Our data also indicate when administered to a patient with a compromised blood-brain barrier, desloratadine may cause sedation. Patients with compromised cardiovascular systems should be closely monitored when administered desloratadine based on our results that desloratadine has the ability to interfere with normal cardiovascular function mediated by muscarinic receptors.

Animals↗

Potent and metabolically stable agonists for protease-activated receptor-2: evaluation of activity in multiple assay systems in vitro and in vivo.

To develop potent and metabolically stable agonists for protease-activated receptor-2 (PAR-2), we prepared 2-furoylated (2f) derivatives of native PAR-2-activating peptides, 2f-LIGKV-OH, 2f-LIGRL-OH, 2f-LIGKV-NH(2), and 2f-LIGRL-NH(2), and systematically evaluated their activity in PAR-2-responsive cell lines and tissues. In both HCT-15 cells and NCTC2544 cells overexpressing PAR-2, all furoylated peptides increased cytosolic Ca(2+) levels with a greater potency than the corresponding native peptides, although a similar maximum response was recorded. The absolute potency of each peptide was greater in NCTC2544, possibly due to a higher level of receptor expression. Furthermore, the difference in potency between the 2-furoylated peptides and the native peptides was enhanced when evaluated in the rat superior mesenteric artery and further increased when measuring PAR-2-mediated salivation in ddY mice in vivo. The potency of 2f-LIGRL-NH(2), the most powerful peptide, relative to SLIGKV-OH, was about 100 in the cultured cell Ca(2+) signaling assays, 517 in the vasorelaxation assay, and 1100 in the salivation assay. Amastatin, an aminopeptidase inhibitor, augmented salivation caused by native peptides, but not furoylated peptides. The PAR-2-activating peptides, including the furoylated derivatives, also produced salivation in the wild-type C57BL/6 mice, but not the PAR-2-deficient mice. Our data thus demonstrate that substitution of the N-terminal serine with a furoyl group in native PAR-2-activating peptides dramatically enhances the agonistic activity and decreases degradation by aminopeptidase, leading to development of 2f-LIGRL-NH(2), the most potent peptide. Furthermore, the data from PAR-2-deficient mice provide ultimate evidence for involvement of PAR-2 in salivation and the selective nature of the 2-furoylated peptides.

Aminopeptidases↗

Classical conditioning of activities of salivary neurones in the cockroach.

Secretion of saliva to aid swallowing and digestion is a basic physiological function found in many vertebrates and invertebrates. For mammals, classical conditioning of salivation in dogs was reported by Pavlov a century ago. However, conditioning of salivation or of related neural activities in non-mammalian species has not been reported. In many species of insects, salivation is regulated by salivary neurones. In this study, we found that salivary neurones of the cockroach Periplaneta americana exhibited a strong response to sucrose solution applied to the mouth and a weak response to odours applied to an antenna, and we studied the effect of conditioning on the activities of salivary neurones. After three sets of differential conditioning trials in which an odour was presented just before the presentation of sucrose solution and the other odour was presented alone, the response of salivary neurones to sucrose-associated odour significantly increased but that to the odour presented alone was unchanged. Backward pairing trials in which an odour was presented after the presentation of sucrose solution were not effective in achieving conditioning. Our study of the change in the level of saliva secretion in response to electrical stimulation of salivary neurones suggested that the magnitude of increase in odour response of salivary neurones by conditioning is sufficient to lead to an increased level of salivation. This study suggests classical conditioning of salivation in an insect.

Animals↗

Acute and long-term effects of thyrotropin releasing hormone on behavior mediated by dopaminergic and cholinergic activities in mice.

Acute and long-term (3 weeks) effects of thyrotropin releasing hormone (TRH) on behavior were investigated in mice. A single injection of TRH produced Straub tail, tremor and salivation, as well as stereotyped responses, such as head bobbing, jaw movement, digging and sniffing. Dose- and time-dependency for the effects of TRH were different depending on each response. A single injection of TRH at a low dose of 2.5 mg/kg SC did not produce stereotypy but this behavior was induced when this dose of TRH was administered in combination with atropine (3 mg/kg IP). In addition, a single low dose of TRH elicited tremor and salivation which were potentiated by physostigmine (0.1 mg/kg IP). A single high dose (20 mg/kg IP) produced marked tremor and salivation which were conversely blocked by atropine. Following daily administration of TRH at a low dose of 2.5 mg/kg SC for 21 days, stereotyped behavior was progressively increased whereas tremor and salivation were decreased. This increase in stereotyped behavior was inhibited by haloperidol (1 mg/kg IP) or physostigmine (0.1 mg/kg IP). When saline was administered instead of TRH for 3 days after long-term administration of TRH, sterotyped behavior was maintained for 2 days but thereafter decreased to some extent. When TRH (1.25 mg/kg SC) was again administered at this stage, there was a marked increase in sterotyped response. These results suggest that TRH induces dopaminergic activation, accompanied by both cholinergic inhibition and cholinergic activation, and that the former is potentiated while the latter is reduced after daily administration of TRH.

Animals↗

Modulation of salivary secretion by acid infusion in the distal esophagus in humans.

To examine the relationship between esophageal acid exposure and development of salivation and heartburn, 15 healthy subjects underwent perfusion of the distal esophagus with varying concentrations of hydrochloric acid, different-osmolality saline solutions, and deionized water. In five study subjects, hydrochloric acid was infused in the body of the stomach only. During the study, timed samples of whole and parotid saliva were collected and analyzed for flow rate and bicarbonate concentration. Only hydrochloric acid concentrations of 20 mmol/L or greater (pH 1.8 or lower) induced a rapid (within 2 minutes) and significant (P < 0.05) increase in salivation. The hydrochloric acid-induced salivation was associated with significant (P < 0.05) increase in bicarbonate secretion in both parotid and whole saliva samples. Intravenous atropine administration completely inhibited hydrochloric acid-induced salivary secretion in all six subjects. Changes in osmolality of saline solution infused in the esophagus and hydrochloric acid infused in the stomach did not significantly alter parotid and whole saliva flow rates. These data suggest that in humans, rapid salivation in response to esophageal mucosal exposure to intraluminal hydrochloric acid is a pH-dependent and osmolality-independent phenomenon that is most likely mediated by pH-sensitive chemoreceptors located in the esophageal mucosa.

Adult↗

Effect of imagining and actually tasting a sour taste on one side of the tongue.

To determine whether images can stimulate brainstem reflexes directly, parotid salivation was measured bilaterally in 24 subjects when they imagined, and actually tasted, a sour taste on one side of the tongue. Salivation increased in both cheeks during unilateral gustatory stimulation; furthermore, the response was greater on the stimulated side than contralaterally, indicating that the gustatory reflex has a unilateral component. Subjects imagined the sour taste more clearly after actually experiencing it. However, salivation did not increase significantly during imagery trials, either before or after exposure to the sour taste; in fact, salivation to imagery decreased below baseline after exposure. These findings suggest that extraneous factors (e.g. the emotional connotations of images, anxiety, discomfort, repetitive measurement or fatigue) might sometimes inhibit specific reflex activity induced by images.

Adolescent↗

Autonomic correlates of alimentary conditioned and unconditioned reactions in the dog.

Analysis of changes in cardiac action and the secretion of saliva during unconditioned alimentary activity in 6 dogs revealed that the beginning of food consumption was accompanied by acceleration of the heart rate (HR) without an increase in salivation. In the course of eating, the heart rate decelerated and salivation increased. Alimentary conditioned stimuli of excitatory (CS+) and inhibitory (CS-) character always produced cardiac acceleration, which in the case of CS+ was accompanied by secretion of saliva. The findings indicate that during food consumption activation of the autonomic system depends upon the contents of motivational processes. In the course of an alimentary act the parasympathetic withdrawal (heart rate acceleration and decrease in salivation) seems to reflect the drive component of the act, while the following parasympathetic activation (heart rate deceleration and increase in salivation) is probably associated with an hedonic component of the consummatory reaction. In our study alimentary conditioned stimuli evoked both drive and hedonic components of alimentary motivation.

Animals↗

Atrial natriuretic factor enhances induced salivary secretion in the rat.

As atrial natriuretic factor (ANF) is intimately involved in water and electrolyte homeostasis, dose-response studies were performed in the parotid as well as submaxillary glands of the rat with increasing doses of the atrial peptide to investigate its possible role as a sialogogic agent. Dose-response studies were also performed in both salivary glands with different pharmacological agonists known to cause salivation in the rat (methacholine, noradrenaline, isoproterenol, methoxamine and substance P) in the absence and in the presence of ANF. The atrial factor did not induce salivation 'per se' at least in the investigated doses. However, it enhanced the salivary response to methacholine, methoxamine and substance P but it did not modify the salivation induced either by noradrenaline or isoproterenol. The present results showed that ANF enhanced the salivation induced by pharmacological agents which stimulate phosphatidylinositol hydrolysis. These effects of ANF may be probably related to the activation of the non-guanylate cyclase coupled receptor which has been associated with phosphatidylinositol turnover. Nevertheless, although the atrial factor induces vasorelaxation, its enhancement of blood flow may not be the major event underlying the present results. The present work suggests a potential physiological role of ANF on the modulation of salivary secretion and provides further evidence on the rol of ANF in the regulation of body fluid homeostasis.

Animals↗

Effects of deprivation on salivary flow in the apparent absence of food stimuli.

Salivation performance in the absence of food-related stimuli was measured with an absorbent technique in 19 subject under no (0-1 h) and moderate (4-6 h) levels of food deprivation. Overall, salivation was reliably (p less than 0.05) greater the higher the hours of deprivation. Results also revealed a reliable positive correlation between hours of deprivation and subjective ratings of hunger. For subjects whose hunger ratings coincided with hours of deprivation, analysis of the salivation data yielded highly reliable (p less than 0.01) differences due to deprivation/hunger. For subjects who reported the same level of hunger at different hours of deprivation, there were no reliable differences in salivation due to deprivation.

Adult↗

Differential urge and salivary responsivity to alcohol cues in alcohol-dependent patients: a comparison of traditional and stringent classification approaches.

Seventy alcohol-dependent individuals were presented with alcohol and water cues on separate trials while salivary responding and self-reported urge for alcohol were measured. Researchers used 2 distinct classification approaches to classify participants as either responders or nonresponders on urge and salivation. Through a traditional classification approach, both urge and salivary responder groups reported higher pleasantness ratings in response to the alcohol cues than nonresponders, yet did not differ on measures of alcohol dependence or withdrawal. Through a more stringent classification approach, salivation responders reported fewer days since their last drink of alcohol and higher pleasantness ratings in response to the alcohol cues than the salivation nonresponder group. The stringently classified urge responders reported higher pleasantness ratings in response to the alcohol cues and more psychiatric distress than the urge nonresponder group. The stringently classified responder groups did not report more alcohol dependence or withdrawal symptoms. There was modest agreement between self-reported urge for alcohol and the physiological measure of salivation. Theoretical and treatment implications are discussed.

Adult↗

Parotid salivary flow in response to mechanical and gustatory stimulation in man.

To examine further the role of the oral receptors in the masticatory-salivary reflex, a study with eight subjects was performed. The influence on mean parotid salivation of combined alterations in frequency and force of chewing and length of the chewing object was evaluated by group comparison. Salivary flow rate was recorded using a sensitive micromanometer, and the frequency (12, 60 and 90 cycles min-1) and force of chewing (10 and 40% of maximum) were controlled by a metronome and masseter muscle EMG, respectively. The maximum instantaneous flow and the latency of the masticatory-salivary reflex were examined in three subjects. For comparison with mean salivation rate during chewing, gustatory stimulation was performed with 0.5 or 5.0% citric acid. The masticatory-salivary reflex was mainly ipsilateral, and depended upon having an object between the teeth. Salivation increased with increases in frequency and force of chewing and with the number of teeth involved, each parameter of chewing having the greatest influence when increased from a low level of action. The salivation response to chewing showed two phases; the first, presumably due to contraction of the myoepithelial cells, had a latency of 0.2-0.4 s, while the second phase occurred about 1 s later. Our results support the hypothesis that the periodontal mechanoreceptors have a major role in the parotid response to chewing. Application of 0.5 and 5.0% citric acid on the back of the tongue induced dose-dependent parotid secretions, significantly higher than those of chewing. A negative correlation was found between the maximum fluid outputs during chewing and 5.0% citric acid stimulation.

Adolescent↗

Myoepithelial cell activation in the submaxillary salivary gland.

1. Pressure in the duct of the submaxillary gland of the cat was recorded under chloralose anaesthesia. Single pulses applied to the parasympathetic nerve caused a pressure rise.2. Salivation was just detectable in about half of the animals when an open tube was connected to the duct and single pulses applied to the nerve. Applying a back pressure of 1-4 mm Hg renders the duct less distensible and under these circumstances secretion of 1-3 mul. fluid was always seen. An alternative method of detecting salivation based on the pressure record itself also showed that salivation occurred in response to the stimulus and that salivation was responsible for the pressure rise observed.3. Single pulses applied to the cervical sympathetic trunk produced a small fall in pressure. In a short series of pulses this was followed by a slow rise which then slowly decayed. It was tentatively concluded that the initial fall was secondary to the accompanying vasoconstriction but the subsequent effects were due to myoepithelial cell contraction.4. Close arterial injection of bradykinin caused a pressure rise which could best be explained by myoepithelial cell contraction.5. It is concluded that the myoepithelial cells of the submaxillary gland of the cat do not receive a parasympathetic motor innervation but it is probable that they are innervated by the sympathetic nervous system and contract in the presence of bradykinin.

Anesthesia, General↗

Alcohol cue reactivity in alcohol-dependent adolescents.

OBJECTIVE: There is substantial evidence that adults with alcohol dependence show different responses (increased craving, increased salivation, changes in heart rate) to alcohol-related stimuli (i.e., alcohol cue reactivity) than nonalcoholics. Alcohol cue reactivity appears to be related to dependence severity and has been used to predict treatment outcomes, where more reactive alcoholics have poorer outcomes than less reactive alcoholics. Adolescents may also develop alcohol dependence, though it is uncertain whether they experience craving and cue reactivity in the presence of alcohol-associated stimuli. METHOD: To examine whether adolescents with alcohol dependence show alcohol cue reactivity, 28 alcoholic adolescents and 25 nonalcoholic adolescents (ages 14-19 years) were compared using a standard cue reactivity procedure, where participants view, hold and sniff different beverages, one of which is their preferred alcoholic beverage. Cue reactivity was assessed with subjective craving ratings, salivation (grams), and heart rate (beats per minute). Analyses were conducted by covarying response to control beverages. RESULTS: Alcoholics responded with both greater craving and greater salivation to the alcohol cue (controlling for response to control cues) than did nonalcoholics, supporting the hypothesis that adolescent alcoholics show alcohol cue reactivity. Heart rate showed no differential cue effect between alcoholics and controls. CONCLUSIONS: Findings support that adolescent alcoholics experience alcohol cue reactivity, as evidenced by increased salivation and subjective craving in the presence of alcohol-related stimuli. Investigation of treatments that may reduce alcohol craving and cue reactivity in adolescents with alcohol dependence is warranted.

Adolescent↗