Changes in striatal electroencephalography and neurochemistry induced by kainic acid seizures are modified by dopamine receptor antagonists.
ABSTRACT We investigated the involvement of striatal dopamine release in electrographic and motor seizure activity evoked by kainic acid in the guinea pig. The involvement of the dopamine receptor subtypes was studied by systemic administration of the dopamine D(1) receptor antagonist, R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH 23390; 0.5 mg kg(-1)), or the dopamine D(2) antagonist, (5-aminosulphonyl)-N-[(1-ethyl-2-pyrrolidinyl)-methyl]-2-methoxybenzamide (sulpiride, 30 mg kg(-1)). Microdialysis and high performance liquid chromatography were used to monitor changes in extracellular levels of striatal dopamine and its metabolites, glutamate, aspartate and gamma-amino-butyric acid (GABA). These data were correlated with changes in the striatal and cortical electroencephalographs and clinical signs. We found that, although neither dopamine receptor antagonist inhibited behavioural seizure activity, blockade of the dopamine D(1)-like receptor with SCH 23390 significantly reduced both the 'power' of the electrical seizure activity and the associated change in extracellular striatal concentration of glutamate, whilst increasing the extracellular striatal concentration of GABA. In contrast, blockade of the dopamine D(2)-like receptor with sulpiride significantly increased the extracellular, striatal content of glutamate and the dopamine metabolites. These results confirm previous evidence in other models of chemically-evoked seizures that antagonism of the dopamine D(1) receptor tends to reduce motor and electrographic seizure activity as well as excitatory amino-acid transmitter activity, while antagonism of the dopamine D(2) receptor has relatively less apparent effect.
- SourceAvailable from: João Pereira Leite[Show abstract] [Hide abstract]
ABSTRACT: INTRODUCTION: Several studies have reported an increased risk for psychiatric disturbances in patients with epilepsy. It is assumed that the risk is higher for patients with partial epilepsy in comparison with patients with idiopathic generalized epilepsy. Besides, the persistence of seizures in some patients and the psychosocial impact of epilepsy seem to be important factors for the increased risk. The symptoms and the underlying psychopathology vary considerably among patients. Psychiatric comorbidities are based on the psychiatric symptomatology, the presence or absence of disturbance of consciousness, the EEG abnormalilies, and in the temporal relation between symptoms and seizures. RESULTS: Psychiatric comorbidities in epilepsy are very common, especially in patients who have the temporal lobe as epileptogenic foci. Psychiatric disorders with a high prevalence in epilepsy include mood disorders such as major depression, anxiety, and psychosis. CONCLUSION: Temporal lobe epilepsy per se cannot be considered a risk factor in developing more or more severe symptoms of psychopathology in patients with partial epilepsy. Concomitant factors, such as the duration of epilepsy and seizure frequency may play an additional role. Better recognition of psychiatric comorbidities will help to develop and implement appropriate diagnostic and treatment programs, and improve functional outcomes and quality of life in people with epilepsy.Journal of Epilepsy and Clinical Neurophysiology 12/2007; 13(4):163-167.
- Journal of Epilepsy and Clinical Neurophysiology 01/2007; 13:163-167.
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ABSTRACT: Alternative splicing is an important mechanism for expanding proteome diversity from a limited number of genes, especially in higher vertebrates. Brain-specific splicing factors play an important role in establishing specific patterns of alternative splicing in the brain and thereby contribute to its complex architecture and function. Nova proteins are splicing factors that are expressed specifically in the central nervous system, where they regulate a large number of pre-mRNAs encoding synaptic proteins that are important for the balance of neuronal excitation and inhibition. Since this balance is interrupted in epileptic seizures, we explored whether LiCl/pilocarpine- or kainate-induced epileptic seizures would induce changes in the levels of Nova mRNAs in the rat brain. We found that the muscarinic agonist, pilocarpine, but not the glutamatergic agonist, kainate, induced a significant downregulation of Nova2 mRNA and upregulation of all three Nova1 mRNA isoforms in the striatum. Treatment with the muscarinic antagonist, scopolamine, at the onset of pilocarpine-induced seizures inhibited the seizures and the changes in Nova mRNA levels. Therefore it seems likely that pilocarpine stimulation of muscarinic acetylcholine receptors was a prerequisite for the observed changes, while the contribution of other striatal neurotransmitter systems activated by seizures could not be excluded. We propose that the LiCl/pilocarpine seizure model could serve as a valuable tool for studying mechanisms of Nova-regulated alternative splicing in rat striatum.Neuroscience 08/2010; 169(2):619-27. · 3.12 Impact Factor