Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present evidence that intermittent administration of nicotine, 2 mg/kg s.c., four times daily to mice for 14 days produces a somatic abstinence syndrome after discontinuing treatment. The nicotine abstinence was mild and protracted, lasting more than 92 h. The constellation of abstinence signs was characterized by rearing, jumping, shakes, abdominal constrictions, chewing, facial tremor and scratching. No autonomic symptomatology was observed. Nicotine abstinence was attenuated with a single dose of nicotine administered at 24 or 48 h into withdrawal. The nicotinic antagonist mecamylamine, 3 mg/kg, induced a small increase in the total abstinence score when given 60 min after the last nicotine injection. Nicotine-abstinent mice displayed reduced locomotor activity. Finally, mice lost weight during the nicotine treatment which was not recovered during the withdrawal. Along with the rat nicotine abstinence model, the mouse model of intermittent nicotine administration and abstinence might be useful for studying the pharmacological and biochemical mechanisms of nicotine addiction and tobacco use.
 ...
PMID:Nicotine abstinence in the mouse. 1062 64

Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting 1 to 3% of individuals over the age of 65 years. While effective therapy exists for treating the bradykinesia, rigidity and tremor associated with the disease, the cause is unknown. There is no treatment available to prevent or slow the progressive neuronal loss in the substantia nigra and associated decreased levels of dopamine in the striatum that underlie the cardinal features of the disease. Both retrospective and prospective epidemiological studies have consistently demonstrated an inverse association between cigarette smoking and PD, leading to theories that smoking in general and nicotine in particular might be neuroprotective. Nicotine has been shown in animals to stimulate the release of dopamine in the striatum, and to preserve nigral neurons and striatal dopamine levels in laboratory animals with lesioned nigrostriatal pathways. Coffee and caffeine consumption have also been shown in epidemiological studies to be inversely related to PD risk. Caffeine is an adenosine A(2A) receptor antagonist that enhances locomotor activity in animal models of parkinsonism. Theophylline, a related compound that has A(2A) receptor blocking properties, has been shown in one small trial to improve motor function in patients with PD. Recently, potent and highly selective A(2A) receptor antagonists have been developed that have demonstrated improvement in motor function in animal models of parkinsonism. Exciting findings are emerging that demonstrate attenuation of dopaminergic neurotoxicity with caffeine and other adenosine receptor antagonists in mice given the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), suggesting that these compounds may be neuroprotective. Evidence for the neuroprotective potential of nicotine and caffeine is compelling, but further work is needed before testing these and related compounds in clinical trials for both individuals at high risk of developing PD and those with early, untreated disease.
 ...
PMID:Current evidence for neuroprotective effects of nicotine and caffeine against Parkinson's disease. 1177 20

We characterized spontaneous and mecamylamine-precipitated nicotine withdrawal using intravenous nicotine self-administration, the acoustic startle response, prepulse inhibition and somatic signs of withdrawal in DBA/2J mice. Nicotine dependence was induced by continuous nicotine infusion through osmotic minipumps. Nicotine self-administration was studied before and after the induction of dependence. The initial test revealed significant nicotine self-administration at the 0.048 microg/infusion dose. During the second self-administration test, saline-treated mice exhibited increased aversiveness of response-contingent infusions of high nicotine doses; these changes were not seen in the nicotine-treated animals reflecting tolerance to nicotine's effects. Neither mecamylamine administration nor spontaneous withdrawal affected the expression of somatic signs, except that increases in jumping were observed during spontaneous withdrawal. Finally, nicotine withdrawal increased general activity in the startle chambers when no stimuli were presented, possibly reflecting increased body tremor and/or agitation, and decreased prepulse inhibition reflecting a sensorimotor gating deficit; the last two effects were reversed by nicotine self-administration. Thus, nicotine withdrawal results in modest, but yet detectable, changes in the behavior of mice.
 ...
PMID:Decreased prepulse inhibition during nicotine withdrawal in DBA/2J mice is reversed by nicotine self-administration. 1286 Apr 78

The aim of this work was evaluate the effects of acute and chronic nicotine pretreatment in the physostigmine-induced tremor in rats. Wistar male rats (3-4 months) were pretreated acutely with different nicotine doses (0, 0.1, 0.5 or 1.0 mg/kg) 10 min before physostigmine (0 and 0.5 mg/kg) treatment and then the tremor was registered by computerized system for 10 min. In another group, rats were pretreated acutely with 0.1 mg/kg of nicotine, recovered at different times (30 or 70 min), and were registered for physostigmine-induced tremor. Nicotine was also used chronically with equal doses for 8 days and recovered at 2, 7 or 21 days before registration of physostigmine-induced tremor. Tremor spectral analysis was performed for amplitude and frequency quantification. Our data show that the acute and chronic nicotine pretreatments alter physostigmine spectrum profile. Nicotine decreased physostigmine-induced tremor amplitude (p<0.05), without changing its tremor frequency. In acutely pretreated rats, recovery experiments showed return of physostigmine-induced tremor for control levels after 70 min, but after 8 days of chronic nicotine pretreatment recovery was delayed 3 weeks. The data analysis shows that acute or chronic nicotine administration can alleviate the physostigmine-induced tremor. Chronic nicotine pretreatment has a long tremor alleviation effect of physostigmine-induced tremor. Possible mechanisms involving the nicotine effects on the physostigmine-induced tremor are discussed.
 ...
PMID:Nicotine pretreatment diminished physostigmine-induced tremor in rats. 1596 16

Stress is a major risk factor in drug addiction development and relapse. Virtually all drugs of abuse act by increasing extracellular dopamine levels in the striatum. To gain an understanding of the interaction between stress and drug exposure, we studied the effects of concomitant chronic nicotine and chronic stress exposure on mouse striatal dopamine levels. C57Bl6/J mice were treated with nicotine in the drinking water or control solution for at least 6 weeks. Some mice were chronically stressed by daily exposure to cold, shaking or restrain. Nicotine-treated mice showed up-regulation of epibatidine binding in several brain regions. In mice treated with both chronic nicotine and stress, epibatidine binding was increased in all studied areas except the dorsal striatum. Therefore, microdialysis was used to measure extracellular dopamine levels in the dorsal striatum of mice chronically treated with nicotine, stress, or both. To have a measure of striatal response to different challenges, we performed microdialysis after acute injection of saline, nicotine, and cocaine. Chronic nicotine enhanced nicotine-dependent dopamine release, while chronic stress blunted the response to cocaine. When mice were subjected to both chronic nicotine and chronic stress, nicotine- and cocaine-dependent dopamine release was undistinguishable from that of control animals. In conclusion, our data suggest that chronic stress and chronic nicotine counteract each other's effect on dopamine release in the striatum. This effect might be mediated by changes in nicotinic acetylcholine receptor up-regulation. This "normalization" of striatal function when both nicotine and stress are present might help explain the comorbidity between stress-related disorders and drug abuse.
 ...
PMID:Opposing actions of chronic stress and chronic nicotine on striatal function in mice. 1853 90

There exists a remarkable diversity of neurotransmitter compounds in the striatum, a pivotal brain region in the pathology of Parkinson's disease, a movement disorder characterized by rigidity, tremor and bradykinesia. The striatal dopaminergic system, which is particularly vulnerable to neurodegeneration in this disorder, appears to be the major contributor to these motor problems. However, numerous other neurotransmitter systems in the striatum most likely also play a significant role, including the nicotinic cholinergic system. Indeed, there is an extensive anatomical overlap between dopaminergic and cholinergic neurons, and acetylcholine is well known to modulate striatal dopamine release both in vitro and in vivo. Nicotine, a drug that stimulates nicotinic acetylcholine receptors (nAChRs), influences several functions relevant to Parkinson's disease. Extensive studies in parkinsonian animals show that nicotine protects against nigrostriatal damage, findings that may explain the well-established decline in Parkinson's disease incidence with tobacco use. In addition, recent work shows that nicotine reduces l-dopa-induced abnormal involuntary movements, a debilitating complication of l-dopa therapy for Parkinson's disease. These combined observations suggest that nAChR stimulation may represent a useful treatment strategy for Parkinson's disease for neuroprotection and symptomatic treatment. Importantly, only selective nAChR subtypes are present in the striatum including the alpha4beta2*, alpha6beta2* and alpha7 nAChR populations. Treatment with nAChR ligands directed to these subtypes may thus yield optimal therapeutic benefit for Parkinson's disease, with a minimum of adverse side effects.
 ...
PMID:Multiple roles for nicotine in Parkinson's disease. 1943 69

Nicotine is widely used in smoking cessation aids. They are marketed in many forms, including: chewing gum, sublingual tablets, lozenges, transdermal patches, cartridges for oral inhalation, and mouth spray. French poison control and toxico-vigilance centres identified 318 cases of exposure to nicotine replacement products in children under the age of 10 years between 2000 and 2010. The exposure provoked symptoms in 62 of these children, about two-thirds of whom were under the age of 4 years. A U.S. analysis identified 1768 cases of poisoning in children under the age of 6 years involving smokeless tobacco products, reported between 2006 and 2008.84% of these cases occurred in children under the age of 3 years. The first signs of nicotine poisoning are gastrointestinal (vomiting, diarrhoea), cardiovascular (tachycardia, hypertension) and neuropsychological (tremor of the extremities). With higher doses, these effects are rapidly followed by loss of consciousness, convulsions or respiratory failure. In children, poisoning can occur after ingestion of 1 mg of nicotine per kilogram of body weight. A dose of this magnitude is sometimes fatal in adults. Most cases of poisoning involving transdermal patches occur when a child finds an unused patch, or a used patch that an adult has discarded in a bin without taking proper precautions. Sometimes they involve patches that have become detached from an adult's skin. In practice, it is important to warn adults using smoking cessation aids containing nicotine that these products are dangerous
 ...
PMID:Nicotine replacement products: poisoning in children. 2492 13


<< Previous 1 2