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)

Buspirone, an azaspirone serotonin (5-HT) 1A partial agonist, has been approved by the FDA as an anxiolytic. It has been tested for use in depression, panic disorder, obsessive-compulsive disorder, and schizophrenia as well. Several trials have indicated that it may prove to be a useful agent for augmentation of other psychotropic medications in these disorders. We review the literature supporting the potential use of buspirone as an augmenting agent.
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PMID:Augmentation with buspirone: a review. 864 75

Genes that regulate serotonergic (5-HT) systems may underlie the etiology of schizophrenia. In this study the gene encoding the 5-HT2A receptor in schizophrenics and healthy controls was examined. First, we sequenced all exons and the flanking introns of the 5-HT2A receptor gene in 10 schizophrenics and 10 controls. The substitution of C for T at position 102 in exon, which had been reported by Warren et al. (1993), was confirmed. Restriction fragment length polymorphism (RFLP) analysis revealed no association between polymorphism and schizophrenia. There was no association between the polymorphism and subdiagnosis, family history, age of onset, amounts of antipsychotics, or positive and negative symptoms before or after medication. Other polymorphisms in the gene were screened in 100 schizophrenics by the single-strand conformation polymorphism method, but none was found. Our results suggest that an abnormality in the 5-HT2A receptor gene in schizophrenia is unlikely.
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PMID:Intact 5-HT2A receptor exons and the adjoining intron regions in schizophrenia. 870 2

Prepulse inhibition (PPI) of an acoustic startle response is impaired in schizophrenics. PPI can also be studied in the rat, and is impaired by dopamine (DA) D2/3 receptor agonists such as apomorphine. This disruption is reversed by DA antagonists, leading to proposals that this approach may be a useful means to identify novel antipsychotics. There is also evidence to suggest a role of serotonergic (5-HT) and glutamatergic systems in schizophrenia, and accordingly PPI can be disrupted by the 5-HT2 agonist DOI, and the non-competitive NMDA antagonist, dizocilpine. In the present study we have examined the effect of four antipsychotic drugs, haloperidol (0.1-0.3 mg/kg), raclopride (0.03-0.3 mg/kg), risperidone (0.3-3 mg/kg) and clozapine (0.0001-10 mg/kg), against the PPI disruptions induced by apomorphine (0.5 mg/kg), DOI (3 mg/kg) and dizocilpine (0.15 mg/kg). Furthermore, these drugs have been examined for their ability to restore a PPI deficit produced by housing rats under conditions of social isolation. All drugs except clozapine reversed an apomorphine-induced disruption. However, clozapine and risperidone, but not raclopride and haloperidol, reversed a DOI-induced disruption. Only risperidone was effective in restoring a PPI deficit produced by dizocilpine. In contrast to the drug-induced disruptions which were differentially sensitive to the various neuroleptics, isolation-induced disruptions were restored by each drug. These results support the idea that non-drug induced disruptions of PPI, such as social isolation, may be a more viable approach to identify novel antipsychotics.
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PMID:Examination of drug-induced and isolation-induced disruptions of prepulse inhibition as models to screen antipsychotic drugs. 871 Oct 60

Serotonin-5-HT1A receptors were measured with [3H]8-hydroxy-2-(di-n-propyl)aminotetralin ([3H]8-OH-DPAT) in postmortem prefrontal cortex of 12 pairs of subjects with schizophrenia and age-matched control subjects. The saturation binding isotherms of [3H]8-OH-DPAT revealed high- and low-affinity binding sites. The density (Bmax) of the high-affinity sites was significantly elevated by an average of 79% in subjects with schizophrenia. The dissociation constant (Kd) of the high-affinity sites in subjects with schizophrenia was not significantly different from the control subjects. These results provide further evidence for a role of the serotonergic system in the pathophysiology of schizophrenia.
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PMID:Serotonin1A receptors are increased in postmortem prefrontal cortex in schizophrenia. 872 Aug 82

Exaggerated intracellular calcium responses to challenges with serotonin (5-HT) have been reported in depression. In our studies, consistent with previous reports, patients with depression exhibited an exaggerated increase in 5-HT-stimulated intracellular calcium concentration ([Ca++]i). Basal cytosolic calcium was elevated in both calcium-free and 1 mM calcium media in depressed patients. the increased responsiveness to 5-HT was seen in both conditions. Patients with schizophrenia and substance abuse did not differ from normal controls. The 5-HT response was correlated with diastolic blood pressure (r = 0.33, p = 0.02): however, this association did not fully account for the exaggerated [Ca++]i responses in the depressed group. These findings suggest that exaggerated increases in [Ca++]i in response to serotonin are a characteristic of depressed patients not shared with schizophrenic and substance abuse patients. The relationship of depression to hypertension, two conditions that share abnormalities of calcium homeostasis, warrants further study.
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PMID:Serotonin-induced increases in platelet cytosolic calcium concentration in depressed, schizophrenic, and substance abuse patients. 873 58

1. Estrogen exerts profound effects on mood, mental state and memory by acting on both "classical" monoamine and neuropeptide transmitter mechanisms in brain. Here we review an example of each type of action. 2. With respect to the effect of estrogen on central monoamine neurotransmission, low levels of estrogen in women are associated with the premenstrual syndrome, postnatal depression and post-menopausal depression. Sex differences in schizophrenia have also been attributed to estrogen. Previous studies have shown that estrogen stimulates a significant increase in dopamine2 (D2) receptors in the striatum. Here we show for the first time that estrogen also stimulates a significant increase in the density of 5-hydroxytryptamine2A (5-HT2A) binding sites in anterior frontal, cingulate and primary olfactory cortex and in the nucleus accumbens, areas of the brain concerned with the control of mood, mental state, cognition, emotion and behavior. These findings explain, for example, the efficacy of estrogen therapy or 5-HT uptake blockers such as fluoxetine in treating the depressive symptoms of the premenstrual syndrome. and suggest that the sex differences in schizophrenia may also be due to an action of estrogen mediated by way of 5-HT2A receptors. 3. With respect to the effect of estrogen on central neuropeptide transmission, estrogen stimulates the expression of the arginine vasopressin (AVP) gene in the bed nucleus of the stria terminalis (BNST) in rodents. This results in a 100-fold increase in AVP mRNA in the BNST and a massive increase in AVP peptide in the BNST and its projections to the lateral septum and lateral habenula. The BNST-AVP system enhances and/or maintains "social" or "olfactory" memory, and thus provides a powerful model for correlating transcriptional control of neuropeptide gene expression with behavior. Whether similar mechanisms operate in the human remain to be determined. 4. These two examples of the action of estrogen on central neurotransmission are discussed in terms of their immediate clinical importance for the treatment of depressive symptoms, their use as powerful models for investigations on the steroid control of central neurotransmitter mechanisms, and the role of estrogen as "Nature's" psychoprotectant.
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PMID:Estrogen control of central neurotransmission: effect on mood, mental state, and memory. 881

1. Considerable efforts have been made in order to develop autoreceptor selective agonists for the treatment of schizophrenia and hyperkinetic disorders. 2. Recent behavioural studies showed that the newly synthesized dopamine lipoamide, N-stearyl dopamine induced a strong hypomotility (-80%) in rats and mice. It is worth noting that this behavioural response was partially antagonized by dopaminergic antagonists, such as haloperidol and sulpiride, administered at doses that block DA autoreceptors. 3. In the present study the authors investigated the neurochemical changes induced by S-DA, in the striatum of the rat brain, in order to estimate a possible correlation between the above mentioned behavioural response and DA metabolism. 4. S-DA (10 or 100 mg/kg, i.p.) induced a significant decrease in DA turnover rate while it did not affect 5-HT metabolism in the striatum. 5. Considering that 5-DA induces a strong hypomotility, which can be partially antagonized by haloperidol or sulpiride administered at low doses, while also decreases the striatal DA turnover rate, it could be suggested that together these findings indicate that this DA lipoamide may be display the characteristics of an antipsychotic agent, acting on the "DA selective" autoreceptors.
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PMID:The neurochemical effects on striatal dopamine turnover rate of N-stearyl dopamine after acute administration in rats. 886 Nov 81

1. Eating disorders can be found in several psychiatric pathologies: schizophrenia, delusional disorder (somatic type), bipolar disorders, major depressive disorder, borderline personality disorder, generalized anxiety disorder, body dysmorphic disorder, somatization disorder and conversion disorder. 2. Although their clinical features have been defined, relatively little is known about the role of neurobiological patterns in the pathogenesis of these disorders. Several CNS neurotransmitters and neuromodulators are involved in the regulation of eating behavior in animals and have been implicated in symptoms such as depression and anxiety often observed in patients with eating disorders. The authors will review some studies on NA, DA, 5-HT, beta-endorphins, CRH, VP, OT, CCK, NPY and PYY involved in eating disorders. Furthermore, we will highlight some of the studies on drug therapy of eating disorders taking into account the effects of these agents on neurotransmitters and neuromodulators. 3. Antidepressant drugs have long been used for anorexia nervosa and bulimia, these disorders been claimed to be affective equivalent. Antidepressant agents seem to be effective in reducing the frequency of binge-eating episodes, purging behavior and depressive symptomatology. It is notable that antidepressant agents have been proved to be effective in patients with chronic bulimic symptoms, even in cases persisting for many years and in patients who had repeatedly failed courses of alternative therapeutic approaches. In all of the positive studies, antidepressant agents appeared effective even in bulimic subjects who did not display concomitant depression. 4. Few controlled studies on use of medications for anorexia nervosa have been published. Central serotonergic receptor-blocking compounds such as cyproheptadine cause marked increase in appetite and body weight. Zinc supplementation or cisapride could be a therapeutic option in addition to psychological and other approaches in anorexia nervosa. 5. There is no therapy as yet which is fully effective in alimentary disorders. Psychotropic drugs give some relief from symptoms, but they cannot cure the disorders. An integrated approach, either pharmacological or psychological, is still recommendable.
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PMID:Neurobiological and psychopharmacological basis in the therapy of bulimia and anorexia. 886 Nov 89

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

The antipsychotic drug risperidone shows high affinity for both central serotonin (5-HT)2A and dopamine (DA)-D2 receptors in vivo. By employing microdialysis in freely moving rats, the effects of acute risperidone administration on regional brain DA and 5-HT release and metabolism were compared with the corresponding effects of the atypical antipsychotic drug clozapine as well as amperozide, the selective DA-D2 receptor antagonist raclopride and the selective 5-HT2A/5-HT2C receptor antagonist ritanserin. Risperidone (0.2 or 2.0 mg/kg, SC) was found to increase DA release and metabolism to about the same extent in three major projection areas of the mesotelencephalic dopaminergic system, i.e. the nucleus accumbens (NAC), the medial prefrontal cortex (MPC) and the lateral striatum (STR). In contrast, clozapine and amperozide (both 10.0 mg/kg, SC), as well as raclopride (2.0 mg/kg, SC), were all found differentially to affect DA release and metabolism in the three projections areas. Specifically, clozapine and amperozide enhanced DA release in the MPC to a greater extent than in the NAC or the STR, whereas raclopride instead preferentially increased DA release in the NAC and the STR but not in the MPC. Ritanserin (3.0 mg/kg, SC) did not exert any major effects on DA metabolism in the three areas studied. In contrast to the regionally rather homogenous activation of brain DA systems caused by risperidone, the drug was found to enhance brain 5-HT metabolism preferentially in the MPC, as indicated by the elevated extracellular concentration of 5-hydroxyindoleacetic acid (5-HIAA) in this region. A similar elevation of the 5-HIAA level in the MPC was observed after amperozide and, to some extent, after clozapine and ritanserin administration. The risperidone-induced (2.0 mg/kg, SC) elevation of 5-HIAA concentrations in the frontal cortex was found to be paralleled by an increased 5-HT release in this brain area. Consequently, our findings demonstrate a pharmacological profile of risperidone, as reflected in brain DA metabolism, in between that of clozapine and the DA-D2 antagonists. The preferential activation of 5-HT release and metabolism in frontal cortical areas might be of particular relevance for the ameliorating effect of risperidone on negative symptoms in schizophrenia, especially when associated with depression.
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PMID:Risperidone: regional effects in vivo on release and metabolism of dopamine and serotonin in the rat brain. 893 2


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