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)

Hypothesized risk factors for psychostimulant, amphetamine, and cocaine abuse include dopamine (DA) receptor polymorphisms, HIV infection, schizophrenia, drug-induced paranoias, and movement disorders; however, the molecular, cellular, and biochemical mechanisms that predispose to drug sensitivity or drive the development of addiction are incompletely understood. Using the Borna disease rat, an animal model of viral-induced encephalopathy wherein sensitivity to the locomotor and stereotypic behavioral effects of d-amphetamine and cocaine is enhanced (Solbrig et al., 1994, 1998), we identify a specific neurotrophin expression pattern triggered by striatal viral injury that increases tyrosine hydroxylase activity, an early step in DA synthesis, to produce a phenotype of enhanced amphetamine sensitivity. The reactive neurotrophin pattern provides a molecular framework for understanding how CNS viral injury, as well as other CNS adaptations producing similar growth factor activation profiles, may influence psychostimulant sensitivity.
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PMID:Neurotrophic factor expression after CNS viral injury produces enhanced sensitivity to psychostimulants: potential mechanism for addiction vulnerability. 1105 Jan 46

Endogenous adenosine in nervous tissue, a central link between energy metabolism and neuronal activity, varies according to behavioral state and (patho)physiological conditions, it may be the major sleep propensity substance. The functional consequences of activation of the four known adenosine receptors, A1, A2A, A2B and A3, are considered here. The mechanisms and electrophysiological actions, mainly those of the A1-receptor, have been extensively studied using in vitro brain-slice preparations. A1-receptor activation inhibits many neurons postsynaptically by inducing or modulating ionic currents and presynaptically by reducing transmitter release. A1-receptors are almost ubiquitous in the brain and affect various K+ (Ileak, IAHP), mixed cationic (Ih), or Ca2+ currents, through activation of Gi/o-proteins (coupled to ion channels, adenylyl cyclase or phospholipases). A2A-receptors are much more localized, their functional role in the striatum is only just emerging. A2B- and A3-receptors may be affected in pathophysiological events, their function is not yet clear. The cAMP-PKA signal cascade plays a central role in the regulation of both neural activity and energy metabolism. Under conditions of increased demand and decreased availability of energy (such as hypoxia, hypoglycemia and/or excessive neuronal activity), adenosine provides a powerful protective feedback mechanism. Interaction with adenosine metabolism is a promising target for therapeutic intervention in neurological and psychiatric diseases such as epilepsy, sleep, movement (parkinsonism or Huntington's disease) or psychiatric disorders (Alzheimer's disease, depression, schizophrenia or addiction).
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PMID:Functions of neuronal adenosine receptors. 1111 31

The prefrontal cortex (PFC) has long been known to be involved in the mediation of complex behavioral responses. Considerable research efforts are directed towards refining the knowledge about the function of this brain area and the role it plays in cognitive performance and behavioral output. In the first part, this review provides, from a pharmacological perspective, an overview of anatomical, electrophysiological and neurochemical aspects of the function of the PFC, with an emphasis on the mesocortical dopamine system. Anatomy of the mesocortical system, basic physiological and pharmacological properties of neurotransmission within the PFC, and interactions between dopamine and glutamate as well as other transmitters within the mesocorticolimbic circuit are included. The coverage of these data is largely restricted to what is relevant for the second part of the review which focuses on behavioral studies that have examined the role of the PFC in a variety of phenomena, behaviors and paradigms. These include reward and addiction, locomotor activity and sensitization, learning, cognition, and schizophrenia. Although the focus of this review is on the mesocortical dopamine system, given the intricate interactions of dopamine with other transmitter systems within the PFC and the importance of the PFC as a source of glutamate in subcortical areas, these aspects are also covered in some detail where appropriate. Naturally, a topic as complex as this cannot be covered comprehensively in its entirety. Therefore this review is largely limited to data derived from studies using rats, and it is also specifically restricted to data concerning the medial PFC (mPFC). Since in several fields of research the findings concerning the function or role of the mPFC are relatively inconsistent, the question is addressed whether these inconsistencies might, at least in part, be related to the anatomical and functional heterogeneity of this brain area.
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PMID:Pharmacology and behavioral pharmacology of the mesocortical dopamine system. 1111 27

A central aim of reformatory efforts, as a consequence of the "Psychiatrieenquete" 1975 (a fundamental report of the situation of psychiatry in Germany), had been dehospitalisation of patients with chronic mental illness and their reintegration into the community. Despite a meanwhile well-developed range of community-based services, patients with severe mental illness only rarely get adequate care by these services. This holds especially true for patients with an unfavourable course of disease such as schizophrenia, severe personality disorder, skid-row alcoholism with multiple problems or for patients with double diagnosis. The reasons are barriers set up by the various services and their underlying concepts as well as structural problems in the health care system. Adapted to the special needs for help of these patients, we present a model for the community-based care of this group, combining elements of community psychiatry, addiction treatment and help for the homeless.
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PMID:[Community-based rehabilitation for severely ill psychiatric patients?]. 1125 50

Literature pertaining to the effects of cannabis use and health which has been published during the past 11 years has been reviewed. Many older concerns about adverse effects on health (chromosomal damage, 'cannabinol psychosis', endocrine abnormalities, cardiac events, impaired immunity) no longer seem to elicit much interest. Continuing concerns about the adverse cognitive effects of chronic use indicate that these can be demonstrated by proper testing; some studies suggest that they may be long-lasting. Although cannabis does not produce a specific psychosis, the possibility exists that it may exacerbate schizophrenia in persons predisposed to that disorder. However, evidence from retrospective surveys must always be questioned. Tolerance and dependence have occurred in man, confirming previous findings in many other species. Addiction tends to be mild and is probably less severe than with other social drugs. Driving under the influence of cannabis is impaired acutely; how long such impairments last is still unknown. More exacting tasks, such as flying an airplane, may be impaired for as long as 24 hours. While there is no doubt that marijuana smoke contains carcinogens, an increase in cancer among users has thus far been anecdotal. Because of the long latent period between cancer induction and initiation of cigarette smoking, the full story is yet to be told. Marijuana use during pregnancy is not advised although the consequences are usually not greater than those of smoking cigarettes, and far less than those from alcohol use. Whether smoked marijuana should become a therapeutic agent requires a cost-benefit analysis of the potential benefits versus the adverse effects of such use as we now know them.
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PMID:Health aspects of cannabis: revisited. 1128 47

The dual diagnosis schizophrenia and addiction represents a combination of an endogenous psychosis and an addictive condition in the sense of abuse of or dependence on psychotropic substances. Before this diagnosis is established, schizophreniform organic psychoses must be distinguished from primary schizophrenia. Since the psychopathological differentiation is often not quite unequivocal, a search must be made for treatable underlying disorders. Here, help is afforded by the patient's history obtained on the basis of the reports of relatives and friends, physical neurologic examinations, and various laboratory, radiologic, electrophysiologic and neuropsychologic methods. In the daily clinical situation, a series of characteristic leading symptoms help clarify the differential diagnosis. The starting point for treatment is the patient's personal view of the problem, and his subjective state of health. Goals to be aimed at include integrative therapeutic approaches propagating the interaction of pharmacotherapy, psychotherapy and sociotherapy.
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PMID:[Schizophrenia and addiction. A frequent psychiatric dual diagnosis]. 1143 63

We have created a transgenic mouse with a hypomorphic allele of the vesicular monoamine transporter 2 (Vmat2) gene by gene targeting. These mice (KA1) have profound changes in monoamine metabolism and function and survive into adulthood. Specifically, these animals express very low levels of VMAT2, an endogenous protein which sequesters monoamines intracellularly into vesicles, a process that, in addition to being important in normal transmission, may also act to keep intracellular levels of the monoamine neurotransmitters below potentially toxic thresholds. Homozygous mice show large reductions in brain tissue monoamines, motor impairments, enhanced sensitivity to dopamine agonism, and changes in the chemical neuroanatomy of the striatum that are consistent with alterations in the balance of the striatonigral (direct) and striatopallidal (indirect) pathways. The VMAT2-deficient KA1 mice are also more vulnerable to the neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in terms of nigral dopamine cell death. We suggest that the mice may be of value in examining, long term, the insidious damaging consequences of abnormal intracellular handling of monoamines. On the basis of our current findings, the mice are likely to prove of immediate interest to aspects of the symptomatology of parkinsonism. They may also, however, be of use in probing other aspects of monoaminergic function and dysfunction in the brain, the latter making important contributions to the pathogenesis of schizophrenia and addiction.
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PMID:Mice with very low expression of the vesicular monoamine transporter 2 gene survive into adulthood: potential mouse model for parkinsonism. 1146 16

Alcoholic patients are frequently regarded as responsible for their alcoholism and alcohol-related diseases, such as liver damage. These patients run the risk of receiving lower medical priority for liver transplantation than patients who are considered as not responsible for their liver damage. However, hardly any scientific research findings support this supposed responsibility of the alcoholic patient for his addiction and the related diseases. Many alcoholic patients have comorbid psychiatric disorders such as antisocial personality disorder, schizophrenia and social phobia, and these cormorbid diseases are often linked specifically and also in a neurobiological way to alcohol abuse. Furthermore, concepts such as responsibility and health have multiple dimensions, which can be contrasted against each other. Useful and fair criteria are presented for the assessment of responsibility for our health.
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PMID:Do alcoholic liver transplantation candidates merit lower medical priority than non-alcoholic candidates? 1149 7

Behavioral sensitization refers to the progressive increase of behavioral responses to psychomotor stimulants, which provides a model for the intensification of drug craving and relapse alleged to underlie addiction in humans. Mechanisms related to sensitization may also contribute to schizophrenia and bipolar disorder. While the phenomenon has been observed for years, only recently have molecular or intracellular mechanisms associated with behavioral sensitization been studied. An overview of cAMP and PLA2 (intracellular, signal transduction mechanisms) relevant to behavioral sensitization will be presented.
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PMID:Signal transduction mechanisms and behavioral sensitization to stimulant drugs: an overview of cAMP and PLA2. 1168 91

Studies showing the presence of glucocorticoids, and their binding sites in the central nervous system indicate that these hormones may affect central neurotransmission. Both, dopaminergic brain system and glucocorticoids are considered to be involved in certain psychopathological conditions in humans, including depression, addiction or schizophrenia. The present study aimed to investigate the influence of glucocorticoids on dopamine agonists-induced stereotyped behavior and locomotor hyperactivity in rats. The results of the experiment demonstrate that prior to administration of prednisolone (4, 6, 10 or 20 mg/kg) or dexamethasone (4 or 8 mg/kg) intensified and prolonged the stereotypy induced by apomorphine (1 mg/kg sc) or amphetamine (2 mg/kg ip). The effect of dexamethasone was more potent. Amphetamine (0.4 mg/kg)- or amantadine (50 mg/kg)-induced locomotor hyperactivity was significantly reduced in rats pretreated with dexamethasone at a dose of 8 mg/kg or 4 mg/kg. Our observations suggest that exogenous glucocorticoids may enhance the activity of the dopaminergic agonists in the striatum but reduce it in the mesolimbic system of rats.
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PMID:Glucocorticoids modulate behavioral effects induced by dopaminergic agonists in rats. 1199 64


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