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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nicotine levels in blood and whole brain were measured as a function of sex and age in C57BL/6J and DBA/2J mice and compared to the behavioral responses following an intraperitoneal injection of nicotine. The results indicate that blood levels of nicotine alone do not accurately predict either brain levels of nicotine or the behavioral responses to a single injection of nicotine. In general, brain levels of nicotine proved to be a fairly accurate predictor of the behavioral responses to nicotine. The data indicate that the sexes differ in their sensitivity to nicotine. Forty-two-day-old male mice of both strains given comparable doses of nicotine were found to concentrate the drug in the brain more than females. However, there was no corresponding increase in sensitivity to this increased brain concentration as measured by LD50, ED50, latency to tremor or latency to death.
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PMID:Relations between nicotine-induced convulsive behavior and blood and brain levels of nicotine as a function of sex and age in two inbred strains of mice. 45 Sep 47

The ontogenetic course of two cholinergically mediated central neuropharmacological effects, yawning and potentiation of head-shaking induced by D-amphetamine (5 mg/kg), was explored in developing rats. Physostigmine (0.1 mg/kg) and pilocarpine (4 mg/kg) evoke stereotyped yawning in neonatal rats, the effect declining in the middle of the second week of life. Both cholinomimetic drugs strongly potentiate amphetamine induced head-shaking between the 4th and 10th postnatal days. Pilocarpine per se is capable of inducing head-shaking, in the absence of amphetamine, in rats from 8 to 12 days. Infant rat yawning and head-shaking are blocked by scopolamine (5 mg/kg). Nicotine (0.1 mg/kg) potentiates head-shaking but inhibits yawning. Yawning is also depressed by D-amphetamine. The early maturation of these cholinergic effects is discussed in comparison to the later maturation of several forebrain cholinergic systems.
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PMID:Ontogeny of two cholinergically mediated central effects: stereotyped yawning and potentiation of head-shaking. 56 22

Cerebral metabolic and behavioral effects of acutely administered nicotine were measured in rats in relation to dose. Nicotine 0.1, 1, or 10 mg/kg or vehicle was administered intraperitoneally to 3-month-old male Fischer-344 rats that had been pretreated with hexamethonium bromide 5 mg/kg i.p. to reduce peripheral autonomic effects. Regional CMRglc (rCMRglc) values were measured, using the quantitative autoradiographic [14C]-2-deoxy-D-glucose method, in 71 brain regions, beginning 3 min after nicotine or vehicle administration. Intensity of body tremor, scored by a blinded rater, was dose related and peaked at 3 min after nicotine injection. rCMRglc rose in a dose-related manner: Nicotine 0.1 mg/kg had no significant effect in any region, whereas 1 mg/kg elevated rCMRglc significantly in 21 regions (mean rise 20%) and 10 mg/kg produced generalized (56 regions) and greater (mean rise 50%) increases in rCMRglc. Nicotine 1 mg/kg activated thalamic nuclei, cerebellum, geniculate nuclei, superior colliculus, median raphe, reticular formation, and the habenulointerpeduncular pathway, but was without effect in the telencephalon. Effects of nicotine in the hindbrain were related anatomically to reported distributions of [3H]nicotine and [3H]acetylcholine but not [125I]alpha-bungarotoxin binding sites, implying that the former ligands label functional nicotine receptors. The pattern of change in rCMRglc after nicotine administration suggests that its cognitive effects in humans are due to augmented arousal/attention and visual processing rather than to direct neocortical or hippocampal activation.
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PMID:Preferential metabolic activation of subcortical brain areas by acute administration of nicotine to rats. 229 36

A 64-year-old carpenter had an unsteady gait, severe dizziness, nocturia, and a loss of erection for more than 4 years. The neurological manifestations consisted of a wide-based ataxic gait, bilateral dysmetria with intentional tremor, staccato speech, rigidity, bradykinesia, and an iris-thinning. There was reproducible orthostatic hypotension. A sweat test revealed severe anhidrosis. Nicotine and methylbenzene sensitivity was absent, whereas norepinephrine infusion test showed a significant elevation of blood pressure. The resting plasma norepinephrine level on recumbency was low and a subnormal surge was noted on standing or exercise. We conclude that the clinical features caused by a degenerative process involving both the central and peripheral autonomic systems, together with atrophy of other systems in this patient, constitute the Shy-Drager syndrome.
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PMID:Abnormal cardiovascular responses to postural changes and pharmacologic agents in a case of Shy-Drager syndrome. 262 36

1. An investigation of central cholinoceptors in the mouse has been made by injecting cholinomimetic drugs into the cerebral ventricles and seeing how their effects were modified by prior administration of atropine-like substances and other drugs.2. Carbachol or oxotremorine injected in small doses intracerebroventricularly into conscious mice caused hypothermia, gross tremor and a variety of parasympathomimetic effects including lachrymation and salivation. Acetylcholine injected in this way was active only in much larger doses.3. Methacholine and pilocarpine also caused a variety of parasympathomimetic effects after intracerebroventricular injection but virtually no hypothermia or tremor.4. Nicotine injected intracerebroventricularly caused mild hypothermia, fine tremor but no parasympathomimetic effects.5. Atropine-like drugs, tricyclic antidepressants and amphetamine antagonized the hypothermia induced by intracerebroventricular carbachol or oxotremorine.6. The sites of action of the atropine-like drugs are in the brain; those of the tricyclic antidepressants and amphetamine are in the periphery probably on heat generating beta-adrenoceptor mechanisms.7. It is concluded that the atropine sensitive cholinoceptors in the brain vary in their sensitivities to cholinomimetic drugs, other than acetylcholine, and may exist in isoreceptor forms.8. Peripheral atropine sensitive cholinoceptors may also exist in isoreceptor forms.
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PMID:Investigation of central cholinergic mechanisms in the conscious mouse. 558 Jun 97

Nicotine (4; 8 mg/kg) given intraperitoneally to mice had a marked hypothermic effect with a duration of more than 2 hours. Mecamylamine (0.5; 2.5 mg/kg) prevented the hypothermic effect of 2 mg/kg nicotine but had no effect on 4 mg/kg nicotine. Atropine (5 mg/kg) did not affect the hypothermia produced by nicotine. Other symptoms induced by nicotine (0.5-4 mg/kg) were convulsions, rigidity, tremor and decrease in motor activity. Pretreatment with mecamylamine (0.5 mg/kg) prevented convulsions but had only a slight effect on the decreased motor activity. Atropine pretreatment was ineffective. It thus seems as if the effects of nicotine at least to some part are mediated by nicotine-like receptors. When a tracer dose of labelled choline (3H-Ch) was given to mice treated with nicotine (4 mg/kg) a marked increase (+100%) in the biosynthesis of labelled acetylcholine (ACh) in the striatum was found when the animals were killed by decapitation. If the mice were killed by a more rapid technique, microwave irradiation of the head, no change in 3H-ACh formation was observed in comparison to controls. The findings indicate that nicotine can preserve a very labile pool of newly synthesized ACh in the striatum.
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PMID:Pharmacodynamic effects of nicotine and acetylcholine biosynthesis in mouse brain. 688 Jul 69

Previous work from this laboratory showed that daily s.c. injections of the organophosphate diisopropylfluorophosphate caused prolonged inhibition of cholinesterase (ChE) activity in whole blood and brain and downregulation of muscarinic receptors in the central nervous system; these changes were accompanied by progressive, persistent deterioration of working memory and motor function. Further, a single s.c. injection of the organophosphate insecticide chlorpyrifos (O,O',-diethyl O-3,5,6-trichloro-2-pyridyl phosphorothionate, CPF), caused neurochemical changes of the same magnitude and duration, but transient impairment of working memory and motor slowing. In the present study, weekly injections of CPF (0, 15, 30 or 60 mg/kg s.c.) inhibited ChE activity in whole blood of rats by 60% to 90% after 5 weeks; the highest dose also induced tremor, working memory impairment and motor slowing in daily delayed matching-to-position/visual discrimination tests. Reducing the CPF injection frequency to every other week relieved the inhibition of whole blood ChE activity (to 50%-75% of control) and ameliorated all the behavioral deficits. Reinstatement of weekly CPF injections (0, 15, 30, or 45 mg/kg) for 10 weeks inhibited whole blood ChE activity by 75% to 90%. Tremor was not observed during this period; however, motor slowing and working memory impairment persisted throughout the dosing period in all treated groups. Pharmacological evidence for tolerance to the muscarinic effects of CPF was observed on trial completion in the daily delayed matching-to-position/visual discrimination task: CPF-treated rats were supersensitive to scopolamine and subsensitive to pilocarpine. Nicotine reversed the reduction in trial completion associated with CPF. Changes in sensitivity to mecamylamine, d-amphetamine and haloperidol were not observed. Taken together, these studies indicate that inhibition of ChE activity by repeated injection of CPF produces a constellation of behavioral effects not evident after a single CPF treatment, even though both treatment regimens caused prolonged inhibition of ChE activity and downregulation of central muscarinic receptors.
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PMID:Repeated inhibition of cholinesterase by chlorpyrifos in rats: behavioral, neurochemical and pharmacological indices of tolerance. 751 12

The rapid secretion of ACTH in response to nicotine is mediated by a central mechanism involving brainstem catecholaminergic regions. To identify specific brainstem regions involved in activating the hypothalamo-pituitary-adrenal axis and other areas of the brain by iv nicotine, immunocytochemical detection of cFos protein was used as a marker for neuronal activation. Nicotine (0.05 mg/kg) stimulated cFos expression in the parvocellular paraventricular nucleus (pcPVN; containing CRH-positive neurons mediating ACTH secretion); this correlated with the expression of cFos in the A2 (norepinephrinergic) and C2 (epinephrinergic) regions of the brainstem nucleus tractus solitarius, which project directly to the pcPVN. The selectivity of this brainstem activation was shown by the absence of responses in the locus coeruleus (LC), A1, and C1 catecholaminergic regions to this low dose of nicotine. In contrast, a high dose of nicotine (0.1 mg/kg), which produced a brief episode of tremor, was required for expression of cFos in the LC. This was associated with a further increase in the number of cFos-positive cells in the PVN, primarily through recruitment in the magnocellular region, a known projection field of LC. The higher dose of nicotine also induced cFos in the vasopressinergic region of the supraoptic nucleus (SON), whereas the lower dose of nicotine exclusively induced cFos in the oxytocinergic region of the SON. Limbic regions that receive catecholaminergic inputs, such as the the central nucleus of the amygdala (involved in PVN regulation) and the cingulate gyrus of the cortex, showed a dose-dependent increase in the number of cFos-positive cells after nicotine, whereas the dentate gyrus of the hippocampus only responded to the high dose. Thus, nicotine is a potent and selective stimulus for neuronal activation in brainstem catecholaminergic regions and their projection fields in the pcPVN and SON, which regulate the hypothalamo-pituitary-adrenal axis and vasopressin/oxytocin secretion, respectively.
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PMID:Nicotine stimulates the expression of cFos protein in the parvocellular paraventricular nucleus and brainstem catecholaminergic regions. 838 11

Smoking a cigarette relieved symptoms in 6 patients with early-onset Parkinson's disease. In these patients smoking reduced tremor, rigidity, bradykinesia, and gait disturbance including frozen gait. These effects lasted for about 10-30 min, and relieved parkinsonian symptoms in the off-period. Nicotine chewing gum had a lesser effect. Nicotine is thought to activate the nigrostriatal dopaminergic pathway and increase the release of dopamine in the striatum, and this can explain the effects of smoking in these patients.
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PMID:Effects of smoking in patients with early-onset Parkinson's disease. 841 63

The nature of the antagonism by anticholinergic compounds of nicotine-induced convulsion in mice has not been defined clearly. Although, because they do not compete effectively for agonist binding to brain tissue in-vitro, these compounds are thought to be non-competitive antagonists in the brain, pharmacological evidence is lacking. This study describes the anti-nicotinic properties of the clinically used anticholinergic antiparkinson drugs, benztropine, biperiden, caramiphen, ethopropazine, procyclidine and trihexyphenidyl. Nicotine-induced convulsion and arecoline-induced tremor in mice were effectively prevented by these drugs. The concentrations of benztropine, biperiden, caramiphen, ethopropazine, procyclidine and trihexyphenidyl affording 50% prevention of nicotine-induced convulsion (ED50 values) were 7.4, 4.6, 7.8, 4.9, 3.1 and 3.3 mg kg(-1), respectively. The classical muscarinic receptor antagonist atropine had potent anti-muscarinic effects but very weak anti-nicotinic activity. The classical nicotinic receptor antagonist mecamylamine had potent anti-nicotinic activity but no anti-muscarinic effects. The pattern of shift of the dose-response curve for nicotine-induced convulsion in mice was determined in the presence of increasing concentrations of the anticholinergic antiparkinson drugs. These drugs were found to increase the ED50 (0.49 mg kg(-1)) of nicotine-induced convulsion in a dose-related manner. The maximum effect of nicotine and the slope of nicotine dose-response curve were not significantly influenced by either low or high doses of benztropine, procyclidine or trihexylphenidyl, which suggests competitive action. Biperiden, caramiphen and ethopropazine, at low doses which significantly increased the ED50 of nicotine, did not affect the maximum effect of nicotine or the slope of the nicotine dose-response curve; at higher doses, however, they reduced the maximum effect and the slope, which suggests that these drugs have both competitive and non-competitive properties in antagonizing nicotine-induced convulsion in mice. The experiments demonstrate that the anticholinergic antiparkinson drugs and mecamylamine effectively antagonize nicotine-induced convulsion, but atropine does not; some of these drugs have competitive properties whereas others seem to have both competitive and non-competitive properties in antagonizing nicotine-induced convulsion in mice.
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PMID:Anti-nicotinic properties of anticholinergic antiparkinson drugs. 987 18


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