Neurotoxicity research
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Neurotoxicity research · Oct 2008
ReviewWhat is the mechanism whereby cannabis use increases risk of psychosis?
Cannabis use has increased greatly over the last three decades. The various types of cannabis differ in their concentration of the main psychoactive component, Delta-9-tetrahydrocannabinol (THC), and the other major ingredient, cannabidiol (CBD). ⋯ It is well known that cannabis intoxication can cause brief psychotic symptoms like paranoia, whilst recent evidence demonstrates that heavy use of cannabis increases the risk of chronic psychoses like schizophrenia; genetic vulnerability seems to predispose some people to a higher risk. This paper starts to consider the neurochemical mechanisms whereby cannabis use increases the risk of psychosis.
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Neurotoxicity research · Oct 2007
Ilex paraguariensis has antioxidant potential and attenuates haloperidol-induced orofacial dyskinesia and memory dysfunction in rats.
Tardive dyskinesia (TD) is a syndrome associated with administration of antipsychotics drugs and may be a consequence of a free radical increase. Ilex paraguariensis (IP), rich in polyphenols, is used to prepare a tea-like beverage, the "mate", and has been investigated for its antioxidant action. Here, we examined the aqueous extract of IP on in vitro TBARS production and in vivo study, using two behavioral models, i.e., haloperidol-induced orofacial dyskinesia (evaluated measuring vacuous chewing movements, VCMs) and memory dysfunction, evaluated in a water-maze task. ⋯ The "mate" prevented the effects of haloperidol in this behavioral paradigm. Our results indicate that IP exhibits an antioxidant role probably related to the presence of polyphenols. The benefit of IP is possibly related to an indirect modulation of oxidative stress.
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Neurotoxicity research · Jul 2007
ReviewComorbidity implications in brain disease: neuronal substrates of symptom profiles.
The neuronal substrates underlying aspects of comorbidity in brain disease states may be described over psychiatric and neurologic conditions that include affective disorders, cognitive disorders, schizophrenia, obsessive-compulsive disorder, substance abuse disorders as well as the neurodegenerative disorders. Regional and circuitry analyses of biogenic amine systems that are implicated in neural and behavioural pathologies are elucidated using neuroimaging, electrophysiological, neurochemical, neuropharmacological and neurobehavioural methods that present demonstrations of the neuropathological phenomena, such as behavioural sensitisation, cognitive impairments, maladaptive reactions to environmental stress and serious motor deficits. Considerations of neuronal alterations that may or may not be associated with behavioural abnormalities examine differentially the implications of discrete areas within brains that have been assigned functional significance; in the case of the frontal lobes, differential deficits of ventromedial and dorsolateral prefrontal cortex may be associated with different aspects of cognition, affect, remission or response to medication thereby imparting a varying aspect to any investigation of comorbidity.
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Neurotoxicity research · Dec 2006
ReviewDopaminergic dysbalance in distinct basal ganglia neurocircuits: implications for the pathophysiology of Parkinson's disease, schizophrenia and attention deficit hyperactivity disorder.
The basal ganglia form a forebrain system that collects signals from a large part of the neocortex, redistributes these cortical inputs both with respect to one another and with respect to inputs from the limbic system, and then focuses the inputs of this redistributed, integrated signals into particular regions of the frontal lobes and brainstem involved in aspects of motor planning and motor memory. Movement disorders associated with basal ganglia dysfunction comprise a spectrum of abnormalities that range from the hypokinetic disorder (from which Parkinson's disease, PD, is the best-known-example) at one extreme to the hyperkinetic disorder (exemplified by Huntington's disease and hemiballism) at the other. In addition to disorders of movement, major mental disorders including schizophrenic-like states and attention deficit hyperactivity disorder (ADHD) have been linked to abnormalities in the basal ganglia and their allied nuclei. ⋯ DAT knockout mice display a phenotype with increased locomotor activity, which is normalized by psychostimulant treatment. Finally, imaging studies demonstrated an increased density of DAT in the striatum of ADHD patients. Which system is disturbed and whether this system is hyper- or hypoactive is not unambiguously known yet.
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Neurotoxicity research · Oct 2006
ReviewDisruption of cortical-limbic interaction as a substrate for comorbidity.
The prefrontal cortex exerts a potent regulatory influence over subcortical systems that are involved in the regulation of affective states. In particular, the amygdala is a region that is known to play a prominent role in the expression of emotions, and this function is believed to be disrupted in affective disorders and drug abuse. In addition, dysfunction of the prefrontal cortex is believed to be a common element in many psychiatric disorders such as schizophrenia. ⋯ In particular, the ability of the prefrontal cortex to modulate amygdala activity is likely to play an important role in our ability to cope with stressors. We propose that a dysfunction within the prefrontal cortex disrupts the ability of this region to effectively modulate the amygdala, leaving the organism susceptible to detrimental effects of stressors. This would appear to be a common underlying process that may leave the individual susceptible to drug abuse and to the onset or exacerbation of psychiatric disorders such as schizophrenia and depression.