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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dopamine projections to the prefrontal cortex are thought to be essential for the proper functioning of this region and are proposed to be involved in negative (deficit) symptomatology of schizophrenia. Our studies in the rodent indicate that clozapine, the most effective antipsychotic drug for the treatment of negative symptoms, causes an increase in the basal output of dopamine neurons projecting to the prefrontal cortex. This finding is in contrast to the effect of clozapine in the basal ganglia and the effect of typical antipsychotic drugs such as haloperidol in the prefrontal cortex. The ability of clozapine to increase dopamine release in the prefrontal cortex and its relatively weak affinity for some types of dopamine receptors suggest that this drug may exert its therapeutic influence in part by increasing dopaminergic function in the prefrontal cortex.
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PMID:Preferential activation of cortical dopamine neurotransmission by clozapine: functional significance. 796 67

Prompt and efficient treatment of acute psychotic episodes combined with the prevention of relapses will limit the accrued morbidity of schizophrenia. However, the heterogeneity of schizophrenia makes it difficult to determine which individuals are most likely to relapse. There are three major potential biological predictors of schizophrenic relapse: (1) behavioral response to dopamine agonist stimulation, (2) the presence of tardive dyskinesia, and (3) increases in anterior pituitary hormones. Dopamine agonists and dopamine antagonist provocative tests, using a single dose of medication, can be used to predict outcome in stabilized schizophrenics undergoing maintenance drug therapy. These tests are indicators of increased dopamine activity, which potentially indicates a worse outcome. This article discusses behavioral response to psychostimulant tests and pituitary hormone levels, particularly growth hormone and prolactin response to dopamine antagonist stimulation. As predictors of outcome, these measures may be useful, clinically, when selecting neuroleptic maintenance schedules, dosage, or withdrawal strategies.
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PMID:Prediction of outcome in first-episode schizophrenia. 809 92

Two factors which seem to have a significant role in schizophrenia are infection and temperature. Evidence is presented that the schizophrenic population may be part of a sub-population which has preferential resistance to epidemic infection. This characteristic alone may not be responsible for vulnerability to schizophrenia. Part at least of the genetic predisposition to schizophrenia may lie in an abnormal response to hormonal disturbances in the intrauterine environment which may result from prenatal viral infection; this abnormal response may cause neurodevelopmental damage. Then in effect the vulnerability of some to schizophrenia will be the cost of population survival in epidemics. Dopamine is involved in central thermoregulation, and may be involved in response to infection. In two inbred mouse strains, one virus-resistant and the other virus-susceptible, there is also a difference in core body temperature response to dopamine. Because of the connection of dopamine sensitivity, temperature and resistance to infection the paired mouse strains are suggested as an animal model for studies relevant to schizophrenia.
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PMID:Schizophrenia, infection and temperature. An animal model for investigating their interrelationships. 839 51

Dopamine receptor dysfunction has been implicated in the pathophysiology of schizophrenia. Schizophrenic patients (n = 76) and control subjects (n = 53) were examined for allele frequencies in a 2-allele BalI polymorphism, causing a serine-->glycine amino acid substitution in the coding sequence of the dopamine D3 receptor gene. No statistical significant differences of allele frequencies or genotype frequencies could be found between the two groups. Neither were there any significant relationships between allele frequencies and a number of clinical variables within the schizophrenic subsample. However, if not corrected for multiple testing, an association was found between homozygosity and positive response to neuroleptic drugs. The present study does not provide evidence that the BalI polymorphism in the dopamine D3 receptor gene is involved in the pathophysiology of schizophrenia. Further investigations with an increased number and variety of patients concerning response to neuroleptic drugs and expression of the receptor in human brain should be performed to definitively exclude this hypothesis.
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PMID:Lack of association between schizophrenia and alleles in the dopamine D3 receptor gene. 851 75

The mesocortical dopamine system is thought to play an important role in the etiology of the stress response. Dopamine (DA) has been shown to accumulate in the rat frontal cortex in response to a wide variety of stressors. Diazepam, an anxiolytic benzodiazepine, can reverse the effects of stress on cortical DA. We investigated the effects of acute and chronic diazepam administration on immobilization stress-induced changes of the DA system in the frontal cortex of the rat. In the first study, 2.5 mg/kg diazepam was administered 20 min prior to 40 min of immobilization stress. Acute diazepam significantly reduced basal levels of extracellular DA and antagonized the stress-induced increase in cortical DA when compared to untreated stressed rats. Acute diazepam did not significantly effect extracellular DOPAC. In the second study, an experimental group of rats was given approximately 2 mg/kg/day diazepam in their drinking water for 3 weeks. This treatment significantly reduced anxiety as assessed by a staircase test for anxiety. Chronic diazepam had no effect on basal levels of cortical DA. However, chronic diazepam treatment also attenuated stress-induced increases in extracellular DA when compared to untreated stressed control rats. Chronic diazepam did not affect stress-induced changes in DOPAC but it did antagonize the effects of stress on HVA. Thus, acute and chronic diazepam treatment can antagonize stress-induced activation of the mesocortical DA system. It is proposed that this effect is produced through an enhancement of GABAergic neurotransmission by diazepam. The role of the dopaminergic system during stress, anxiety, and schizophrenia is discussed.
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PMID:The effect of acute and chronic diazepam treatment on stress-induced changes in cortical dopamine in the rat. 858 19

Dopamine receptors are the principal targets of drugs used in the treatment of schizophrenia. Among the five mammalian dopamine-receptor subtypes, the D4 subtype is of particular interest because of its high affinity for the atypical neuroleptic clozapine. Interest in clozapine stems from its effectiveness in reducing positive and negative symptoms in acutely psychotic and treatment-resistant schizophrenic patients without eliciting extrapyramidal side effects. We have produced a subtype-specific antibody against the D4 receptor and localized it within specific cellular elements and synaptic circuits of the central nervous system. The D4-receptor antibody labelled GABAergic neurons in the cerebral cortex, hippocampus, thalamic reticular nucleus, globus pallidus and the substantia nigra (pars reticulata). Labelling was also observed in a subset of cortical pyramidal cells. Our findings suggest that clozapine's beneficial effects in schizophrenia may be achieved, in part, through D4-mediated GABA modulation, possibly implicating disinhibition of excitatory transmission in intrinsic cortical, thalamocortical and extrapyramidal pathways.
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PMID:Localization of dopamine D4 receptors in GABAergic neurons of the primate brain. 862 68

In this paper schizophrenia is taken to be a collection of diseases with similar pathological features, including the core Bleulerian symptoms. The aim is to see how far current research can specify the anatomical regions which are functionally defective in schizophrenia and what transmitter systems may be involved. It appears schizophrenic brains show a tendency toward fewer cells in the temporal region, including limbic system as well as the thalamus. Functional deficits are seen in the dorsolateral frontal cortex, as well as thalamus suggesting a cortical-thalamic-striatal pathway. It is clear that Dopamine disregulation in this pathway leads to psychotic symptoms but probably does not account for the ambivalence, affective blunting or asocial behavior. GABA lesions prenatally could lead to glutamate over activity with potential toxic consequences after puberty leading to a plausible hypothesis as to the central neurochemical defect in schizophrenia, this hypothesis is elaborated.
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PMID:[Neurobiology of schizophrenia]. 865 3

Although it is unlikely that the different types of course and severity of schizophrenia are caused by one neurochemical abnormality alone, indirect pharmacological evidence still suggests a relative excess of dopaminergic activity being implicated in the pathogenesis of most of the schizophrenic symptoms, e.g. positive symptomatology. Synthesis and release of dopamine as well as firing rates of dopaminergic neurons are controlled by stimulation of autoreceptors via a negative feedback regulation. Investigations on therapeutic effects of autoreceptor-nonselective dopamine agonists in schizophrenia have yielded inconsistent results. Dopamine autoreceptor agonists like pramipexole, roxindole, talipexole and OPC-4392 as well as partial agonists like terguride and SDZ HDC 912 have been tested in positive schizophrenic symptomatology in order to reduce the postulated excess of central dopaminergic activity. However, administration of autoreceptor-'selective' agonists did not result in a significant improvement of positive symptoms. In predominantly negative schizophrenic symptomatology, a dopamine deficit rather than an excess has been hypothesized. Consequently, a nonselective dopamine agonistic action could be effective in some negative symptoms. Current evidence from several open and one placebo-controlled clinical trial suggests that some dopamine autoreceptor agonists like pramipexole, roxindole and talipexole may produce a mild improvement of symptoms like affective flattening, depressed mood, alogia and avolition. Nevertheless, these findings do not yet allow a reliable judgement and remain to be clarified by further double-blind placebo-controlled studies over a sufficient treatment duration.
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PMID:Dopamine agonists in schizophrenia: a review. 877 58

1. The ventral tegmental area (VTA) has been implicated in both the rewarding effects of drugs of abuse and the etiology of schizophrenia. We report here that serotonin (5-HT) potentiates the inhibitory effect of dopamine on dopaminergic VTA neurons. Dopamine (0.5-10 microM) inhibited the spontaneous firing of putative dopamine-containing neurons of the VTA. 5-HT (5-10 microM) itself did not significantly alter the spontaneous firing rate; however, in the presence of 5-HT, the inhibitory potency of dopamine was significantly increased. 2. The inhibitory potency of the dopamine agonist quinpirole was also increased by 5-HT. 3. 5-HT-induced potentiation was also produced by the selective 5-HT2 agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine, and was reversed by the selective 5-HT2 antagonist ketanserin. 4. This novel action of 5-HT on dopaminergic neurons has important implications for the development of drugs to treat schizophrenia, and for the identification of agents that will be useful in treating drug abuse disorders like alcoholism.
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PMID:Serotonin potentiates dopamine inhibition of ventral tegmental area neurons in vitro. 889 Mar 16

Prepulse inhibition (PPI) of the acoustic startle reflex, a measure of sensory gating, is reduced in schizophrenic patients. Dopamine agonists and NMDA receptor antagonists such as phencyclidine (PCP) can disrupt PPI in animals, consistent with both the dopamine and glutamate hypotheses of schizophrenia. In this study, we sought to further characterize the effects of the NMDA antagonist dizocilpine on acoustic startle modulation. Fischer 344 rats were tested after one of three doses of dizocilpine (0.05, 0.2, and 0.5 mg/kg) and assessed for PPI as well as for alterations in baseline startle and prepulse facilitation (PPF). Results showed complete disruption of PPI for each inhibitory trial type after 0.2 and 0.5 mg/kg of dizocilpine. Baseline startle and PPF were enhanced by the low dose but decreased with the moderate and high doses of dizocilpine. Although dizocilpine caused alterations in prepulse modulation of startle similar to dopamine agonists, some effects differ. Unique effects of dizocilpine on sensory gating are discussed in terms of their potential for discriminating subtypes of schizophrenic illness with different underlying pathophysiology.
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PMID:Effects of the PCP analog dizocilpine on sensory gating: potential relevance to clinical subtypes of schizophrenia. 889 67


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