Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nicotine-induced dopamine (DA) release constitutes a pharmacological probe of the DA system that has potential use in patients with schizophrenia, who have abnormally elevated DA release after amphetamine administration and possibly abnormalities in nicotinic signaling. We performed positron emission tomography studies in five rhesus monkeys that received i.v. nicotine doses ranging from 0.01 to 0.06 mg/kg. [(11)C]raclopride was administered with either a bolus plus constant infusion or with paired bolus injections. The dynamics of D-2-binding potential (BP) after nicotine administration were studied and compared to amphetamine. Nicotine caused a significant albeit small reduction (5%, p<0.03) in BP, regardless of methodology of tracer administration. This effect disappeared 2.5 h after nicotine administration. Amphetamine caused much larger and prolonged displacement of [(11)C]raclopride as compared to nicotine. There was no correlation between changes in BP and nicotine dose or plasma level. Regional differences in the nicotine effect within the basal ganglia were not found. Our data are consistent with the increase in DA detected with microdialysis in animals after acute nicotine administration, however, a larger effect size would be desirable to attempt studies comparing human smokers with and without schizophrenia.
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PMID:Nicotine-induced dopamine release in primates measured with [11C]raclopride PET. 1466 15

Patients with schizophrenia and related psychoses frequently use, abuse and become dependent on psychoactive substances. Local surveys indicate differences in both types and patterns of substances used. A cross-sectional survey was conducted to document abuse in 207 successive outpatients presenting to a psychiatric continuing care facility in a large Canadian city. Nicotine, alcohol and cannabis were the most frequently abused substances in the cohort. Excluding nicotine, 44.9% met criteria for lifetime and 14.0% for current abuse/dependence. Cocaine, heroin, hallucinogen, amphetamine, and inhalant use were rarely reported. Patients with current substance abuse/dependence and a psychotic disorder (dual diagnosis, DD) had significantly higher Positive and Negative Symptom Scale (PANSS) positive scores than lifetime-DD or those with a single diagnosis (SD). Significantly more current-DD (69.0%) patients were depressed (HAM-D score > or =12) compared to SD (45.6%). Furthermore, current-DD (27.6%) patients were more likely than SD (4.5%) to be medication non-compliant. Patients with current-DD were more likely to smoke cigarettes (88.9%) compared to those with SD (49.6%) and they had significantly longer histories of cigarette smoking (19.1 for DD vs. 11.5 years for SD). The smoking behavior of the DD population is discussed in terms of enhanced risk for alcohol abuse, as well as effects on antipsychotic blood levels and metabolism.
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PMID:Drug and alcohol use among patients with schizophrenia and related psychoses: levels and consequences. 1498 74

Schizophrenia patients may exhibit high tobacco smoking rates in part to self-medicate sensory gating deficits with nicotine contained in tobacco. To test this hypothesis, we induced sensori-motor gating deficits in four mouse strains with phencyclidine, a noncompetitive antagonist of glutamatergic N -methyl-d-aspartate receptors. Nicotine attenuated the disruption in prepulse inhibition induced by phencyclidine in DBA/2J and C3H/HeJ but not in C57BL/6J or 129T2/SvEmsJ mice. These results highlight genetic variations in the regulation by nicotinic cholinergic systems of the dysfunction in glutamatergic transmission contributing to gating deficits in schizophrenia. Further, these findings support the hypothesis of self-medication of gating deficits in schizophrenia through tobacco smoking, and suggest that treatments targeting genetic dysfunctions in nicotinic-glutamatergic interactions that would treat cognitive deficits will assist schizophrenia patients in minimizing tobacco smoking.
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PMID:Strain-specificity in nicotine attenuation of phencyclidine-induced disruption of prepulse inhibition in mice: relevance to smoking in schizophrenia patients. 1499 Aug 73

Nicotine addiction is the single largest preventable cause of morbidity and mortality in the Western World. Smoking is not any more just a bad habit, but a substance addiction problem. The pharmacological aspects of nicotine show that this substance has a broad distribution in the different body compartnents, due mainly to its lipophilic characteristic. There are nicotinic receptors as members of cholinergic receptors' family. They are located in neuromuscular junction and in the central nervous system (CNS). Although they are similar, pentameric structure with an ionic channel to sodium, there are some differences in the protein chains characteristics. Repeated administration of nicotine in rats, results in the sensitization phenomenon, which produces increase in the behavioral locomotor activity response. It has been found that most psychostimulants-induced behavioral sensitization through a nicotine receptor activation. Nicotine receptors in CNS are located mainly in presynaptic membrane and in that way they regulated the release of several neurotransmitters, among them acetylcholine, dopamine, serotonin, and norepinephrine. In some activities like sleep-wake cycle, nicotine receptors have a functional significance. Nicotine receptor stimulation promotes wake time, reduces both, total sleep time and rapid eye movement sleep (REMS). About nicotine dependence, this substance full fills all the criteria for dependence and withdrawal syndrome. There are some people that have more vulnerability for to become nicotine dependent, those are psychiatric patients. Among them schizophrenia, major depression, anxiety disorders and attention deficit disorder, represent the best example in this area. Nicotine may have some beneficial effects, among them are some neuroprotective effects in disorders like Parkinson's disease, and Gilles de la Tourette' syndrome. Also there are several evidences that support the role of nicotine in cognitive improvement functions like attention, concentration, and memory. Finally there are several strategies to deal with nicotine dependence, Nicotine Replacement Therapy (NRT), which are nicotine chewing-gum, transdermal nicotine patches, and nicotine inhalators device. Also some antidepressants like bupropion has shown to be effective in smoking cessation treatment. To know more about nicotine phenomenon would be important, because that will allow a more mature perspective about the damage and beneficial effects of that substance.
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PMID:Nicotine dependence and psychiatric disorders. 1501 38

Nicotine and/or smoking have been shown to reduce various cognitive deficits associated with schizophrenia. Here, we examine the effects of nicotine gum on repeated performance on a simple eye movement task. Eight schizophrenic subjects and eight controls participated in three days of testing on saccade (S) and antisaccade (AS) tasks. On each testing day, subjects participated in four testing sessions and received both of two nicotine gum treatments (4 and 6 mg) and both of two control conditions (placebo gum and no gum), each followed by a recovery period. Overall, schizophrenics showed significant impairments on the AS task. However, upon individual examination only four schizophrenics showed significant differences in AS errors or reaction times (RTs) when compared to controls. The other four schizophrenic subjects showed control level performance. All schizophrenic subjects showed normal and better than control level performance on the simple S task. Furthermore, no effects of nicotine were seen on the simple S task. There were significant treatment effects on the AS task. Nicotine treatment significantly decreased errors in the task impaired schizophrenic group and this effect was most pronounced at the 6 mg level. No nicotine effects were demonstrated for non-impaired schizophrenic subjects or controls. This study demonstrates a benefit of short exposure to nicotine in cognitively impaired schizophrenic subjects. These results support previous findings of cognitive benefits of nicotine in schizophrenics.
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PMID:Nicotine reduces antisaccade errors in task impaired schizophrenic subjects. 1509 58

Several lines of evidence suggest a pathophysiological role for nicotinic receptors in schizophrenia. Activation by nicotine alters physiological dysfunctions, such as eye movement and sensory gating abnormalities, but effects on neuropsychological performance are just beginning to be investigated. Nicotine-induced desensitization and the well-known tachyphylaxis of nicotinic receptors may confound such efforts. In all, 20 schizophrenics, 10 smokers, and 10 nonsmokers were assessed following the administration of nicotine gum and placebo gum. The Repeatable Battery for the Assessment of Neuropsychological Status was administered. Nicotine affected only the Attention Index; there were no effects on learning and memory, language, or visuospatial/constructional abilities. Attentional function was increased in nonsmokers, but decreased in nicotine-abstinent smokers after nicotine administration. The effects of nicotine in schizophrenia do not extend to all areas of cognition. Effects on attention may be severely limited by tachyphylaxis, such that decremented performance occurs in smokers, while modest effects may be achieved in nonsmokers.
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PMID:Effects of nicotine on cognitive deficits in schizophrenia. 1513 35

Following exocytotic release of the biogenic amine neurotransmitters, norepinephrine and dopamine, are removed from the synaptic cleft by the respective transporter, norepinephrine transporter (NET) and dopamine transporter (DAT) located on the plasma membrane. The catecholamine transporters are the molecular targets for psychoactive drugs as well as drugs of abuse such as cocaine and amphetamine and the Parkinsonism-inducing neurotoxin, MPP+. Nicotine regulates the transport of catecholamines and MPP+ and may exert self-medicating effects for depression, schizophrenia and attention deficit hyperactivity disorder, and neuroprotective effects against MPP+ through the regulation of the transporters. The availability of cDNAs of these transporters has permitted detailed pharmacological studies in heterologous expression systems for determining the mechanisms of action of nicotine on transporters. Moreover, functional analysis of the effect of single amino acid substitution suggests that specific residues in DAT molecules may play a significant role in interaction with MPP+ and cocaine, and thus would promise a development of novel drugs with diverse chemical structures.
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PMID:Regulation of dopamine and MPP+ transport by catecholamine transporters. 1516 8

Nicotine has been reported to normalize deficits in auditory sensory gating in the cases of schizophrenia, suggesting an involvement of nicotinic acetylcholine receptors in attentional abnormalities. However, the mechanism remains unclear. The present study investigated the effects of nicotine on the disruption of prepulse inhibition (PPI) of the acoustic startle response induced by apomorphine or phencyclidine in rats. Over the dose range tested, nicotine (0.05-1 mg kg(-1), s.c.) did not disrupt PPI. Neither methyllycaconitine (0.5-5 mg kg(-1), s.c.), an alpha(7) nicotinic receptor antagonist, nor dihydro-beta-erythroidine (0.5-2 mg kg(-1), s.c.), an alpha(4)beta(2) nicotinic receptor antagonist, had any effect on PPI. Nicotine (0.01-0.2 mg kg(-1), s.c.) dose-dependently reversed the disruption of PPI induced by apomorphine (1 mg kg(-1), s.c.), but had no effect on the disruption of PPI induced by phencyclidine (2 mg kg(-1), s.c.). The reversal of apomorphine-induced PPI disruption by nicotine (0.2 mg kg(-1)) was eliminated by mecamylamine (1 mg kg(-1), i.p.), but not by hexamethonium (10 mg kg(-1), i.p.), indicating the involvement of central nicotinic receptors. The antagonistic action of nicotine on apomorphine-induced PPI disruption was dose-dependently blocked by methyllycaconitine (1 and 2 mg kg(-1), s.c.). However, dihydro-beta-erythroidine (1 and 2 mg kg(-1), s.c.) had no effect. These results suggest that nicotine reverses the disruption of apomorphine-induced PPI through central alpha(7) nicotinic receptors.
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PMID:Nicotine blocks apomorphine-induced disruption of prepulse inhibition of the acoustic startle in rats: possible involvement of central nicotinic alpha7 receptors. 1519 6

A retrospective case series of 12 smokers with schizophrenia or schizoaffective disorder who had not successfully quit smoking with previous treatments for tobacco dependence were treated with nicotine nasal spray. All but one patient (92 percent) tolerated the nasal spray well, and nine (75 percent) used it at maximal doses for prolonged periods. After treatment five patients (42 percent) were abstinent from smoking for more than 90 days, and four patients (33 percent) substantially reduced the amount that they smoked. Ten patients (83 percent) used the spray in combination with other medications, and all received psychosocial support. Nicotine nasal spray was found to be well tolerated.
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PMID:A case series of nicotine nasal spray in the treatment of tobacco dependence among patients with schizophrenia. 1534 71

The pros and cons of N-methyl-D-aspartate (NMDA) antagonists as drug models of schizophrenia are discussed in relation to the neuropathology of this complex mental spectrum of diseases. The role of acetylcholine, dopamine, gamma aminobutyric acid, glutamic acid, and serotonin emphasizes that multiple neurotransmitter system abnormalities are involved, even though current drug therapy involves primarily dopamine (D(2))/serotonin (5 HT(2)) antagonists. Only some of the fundamental aspects of schizophrenia are replicated by NMDA receptor antagonists of glutamic acid. Subchronic NMDA antagonism in an animal model results in decreased levels of dopamine in prefrontal cortex and increased D(1) receptor binding. The results of PET studies of schizophrenic patients imply decreased dopamine levels in their prefrontal cortex. Tobacco-smoking schizophrenic patients transiently normalize prepulse inhibition. Nicotine appears to be one factor that may help explain some of these phenomena.
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PMID:N-methyl-D-aspartate antagonists as drug models of schizophrenia: a surprising link to tobacco smoking. 1536 4


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