Cortical and hippocampal EEG effects of neurotransmitter agonists in spontaneously hypertensive vs. kainate-treated rats

To analyze mediatory mechanisms underlying attention-deficit hyperactivity disorder (ADHD) and their association with epilepsy, the electroencephalogram (EEG) responses to various centrally applied neurotransmitter agonists were studied in spontaneously hypertensive (SH), kainate-treated (KA), and normotensive (control) rats, with chronically implanted electrodes into the frontal cortex and hippocampus and a cannula into the lateral cerebral ventricle. In SH rats, the baseline EEG showed increased delta and beta2 activity in the hippocampus and decreased alpha/beta1 activity in both brain areas. In KA rats, these delta and alpha/beta1 effects were observed 2 weeks post-kainate, while the beta2 activity increase occurred after 5 weeks in the hippocampus and, to a greater extent, 9 weeks post-injection in both brain areas. In SH rats, NMDA increased delta and decreased alpha/beta1 activity, similar to KA rats 5 weeks post-injection. In SH rats, clonidine augmented theta/beta2 increase in the cortex and alpha suppression in both brain areas, in parallel with induction of beta2 activity in the hippocampus. These beta2 effects were observed 5 and 9 weeks post-kainate. In SH rats, baclofen produced robust delta/theta enhancement and alpha/beta1 suppression in both brain areas, with additional beta2 activity increase in the hippocampus, while muscimol was ineffective in both groups of rats. In KA rats, EEG responses to GABA agonists were similar to those in control. Our results demonstrate sensitization of NMDA receptors and α2-adrenoceptors both in SH and KA rats and that of GABAb receptors specifically in SH rats.

[1]  R. Cannon,et al.  Reduced Mg2+ blockade of synaptically activated N-methyl-d-aspartate receptor-channels in CA1 pyramidal neurons in kainic acid-lesioned rat hippocampus , 1999, Neuroscience.

[2]  L. Pellegrino,et al.  stereotaxic atlas of the rat brain , 1967 .

[3]  M. Reilly,et al.  Response acquisition with delayed reinforcement in a rodent model of attention-deficit/hyperactivity disorder (ADHD) , 2006, Behavioural Brain Research.

[4]  L. Solberg,et al.  Paradoxical Hormonal and Behavioral Responses to Hypothyroid and Hyperthyroid States in the Wistar–Kyoto Rat , 2001, Neuropsychopharmacology.

[5]  K. M. Clements,et al.  Spontaneously hypertensive, Wistar Kyoto and Sprague–Dawley rats differ in their use of place and response strategies in the water radial arm maze , 2007, Neurobiology of Learning and Memory.

[6]  Jaroslaw Harezlak,et al.  ADHD and epilepsy in childhood. , 2003, Developmental medicine and child neurology.

[7]  C. J. Landmark,et al.  Antiepileptic Drugs in Non-Epilepsy Disorders , 2012 .

[8]  D. Viggiano,et al.  Involvement of Norepinephrine in the Control of Activity and Attentive Processes in Animal Models of Attention Deficit Hyperactivity Disorder , 2004, Neural plasticity.

[9]  Y Ohta,et al.  TEMPORAL AND SPATIAL PROPERTIES OF SLOW WAVES IN THE ELECTROENCEPHALOGRAM OF SPONTANEOUSLY HYPERTENSIVE RATS , 1995, Clinical and experimental pharmacology & physiology. Supplement.

[10]  F. Dudek,et al.  Electrographic Seizures and New Recurrent Excitatory Circuits in the Dentate Gyrus of Hippocampal Slices from Kainate-Treated Epileptic Rats , 1996, The Journal of Neuroscience.

[11]  M. Herrmann,et al.  Increased EEG power density in alpha and theta bands in adult ADHD patients , 2008, Journal of Neural Transmission.

[12]  Y. Ben-Ari,et al.  Operative GABAergic inhibition in hippocampal CA1 pyramidal neurons in experimental epilepsy. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[13]  S. Faraone,et al.  Molecular genetics of attention deficit hyperactivity disorder. , 2010, The Psychiatric clinics of North America.

[14]  V. Russell,et al.  Increased noradrenergic activity in prefrontal cortex slices of an animal model for attention-deficit hyperactivity disorder — the spontaneously hypertensive rat , 2000, Behavioural Brain Research.

[15]  A. Arnsten,et al.  Locomotor hyperactivity induced by blockade of prefrontal cortical α2-adrenoceptors in monkeys , 2005, Biological Psychiatry.

[16]  V. Russell,et al.  Glutamate-stimulated release of norepinephrine in hippocampal slices of animal models of attention-deficit/hyperactivity disorder (spontaneously hypertensive rat) and depression/anxiety-like behaviours (Wistar–Kyoto rat) , 2008, Brain Research.

[17]  K. Starke,et al.  Protection of presynaptic α-adrenoceptors against irreversible blockade by phenoxybenzamine: preservation of the modulatory effects of exogenous noradrenaline and yohimbine , 1987, Naunyn-Schmiedeberg's Archives of Pharmacology.

[18]  W. Hauser,et al.  ADHD as a risk factor for incident unprovoked seizures and epilepsy in children. , 2004, Archives of general psychiatry.

[19]  Mehdi Farshbaf,et al.  Rodent Models of Attention-Deficit/Hyperactivity Disorder , 2005, Biological Psychiatry.

[20]  T L Babb,et al.  Hippocampal EEG excitability and chronic spontaneous seizures are associated with aberrant synaptic reorganization in the rat intrahippocampal kainate model. , 1993, Electroencephalography and clinical neurophysiology.

[21]  C. Johannessen Landmark,et al.  Antiepileptic drugs in non-epilepsy disorders: relations between mechanisms of action and clinical efficacy. , 2008, CNS drugs.

[22]  D A Turner,et al.  Excitatory synaptic potentials in kainic acid-denervated rat CA1 pyramidal neurons , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[23]  V. Russell,et al.  The control of responsiveness in ADHD by catecholamines: evidence for dopaminergic, noradrenergic and interactive roles. , 2005, Developmental science.

[24]  J. Harezlak,et al.  ADHD and epilepsy in childhood , 2003 .

[25]  V. V. Vorob’ev,et al.  Analysis of electroencephalograms using a modified amplitude-interval algorithm , 1999, Neuroscience and Behavioral Physiology.

[26]  S. Pliszka The Neuropsychopharmacology of Attention-Deficit/Hyperactivity Disorder , 2005, Biological Psychiatry.

[27]  J. Smoller,et al.  Molecular Genetics of Attention-Deficit/Hyperactivity Disorder , 2005, Biological Psychiatry.

[28]  D. Heal,et al.  New perspectives from microdialysis studies in freely-moving, spontaneously hypertensive rats on the pharmacology of drugs for the treatment of ADHD , 2008, Pharmacology Biochemistry and Behavior.

[29]  W. Singer,et al.  Synchronization of oscillatory neuronal responses in cat striate cortex: Temporal properties , 1992, Visual Neuroscience.

[30]  Mark Sadler,et al.  Electroencephalographic Features of Temporal Lobe Epilepsy , 2010, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[31]  M. Tantucci,et al.  EEG Power Spectra Changes and Forebrain Ischemia in Rats , 2003, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[32]  N. Lazarov,et al.  Diurnal rhythms of spontaneous recurrent seizures and behavioral alterations of Wistar and spontaneously hypertensive rats in the kainate model of epilepsy , 2010, Epilepsy & Behavior.

[33]  O. Hvalby,et al.  N-methyl-d-aspartate receptor subunit dysfunction at hippocampal glutamatergic synapses in an animal model of attention-deficit/hyperactivity disorder , 2009, Neuroscience.

[34]  R. Hall,et al.  Organization of motor and somatosensory neocortex in the albino rat , 1974 .

[35]  E. Bertram,et al.  Different reactions of control and epileptic rats to administration of APV or muscimol on thalamic or CA3-induced CA1 responses. , 2003, Journal of neurophysiology.

[36]  L. Dwoskin,et al.  Advancing the spontaneous hypertensive rat model of attention deficit/hyperactivity disorder. , 2008, Behavioral neuroscience.

[37]  Luigi Barberini,et al.  Beta and Gamma Range EEG Power‐Spectrum Correlation with Spiking Discharges in DBA/2J Mice Absence Model: Role of GABAB Receptors , 2006, Epilepsia.

[38]  J. Villemure,et al.  Excitatory Amino Acids Modulate Phosphoinositide Signal Transduction in Human Epileptic Neocortex , 1992, Epilepsia.

[39]  Sandra K Loo,et al.  Clinical Utility of EEG in Attention-Deficit/Hyperactivity Disorder: A Research Update , 2005, Neurotherapeutics.

[40]  V. Russell,et al.  NMDA Receptor Function in the Prefrontal Cortex of a Rat Model for Attention-Deficit Hyperactivity Disorder , 2004, Metabolic Brain Disease.

[41]  M. Holtmann,et al.  Role of electroencephalography in attention-deficit hyperactivity disorder , 2006, Expert review of neurotherapeutics.

[42]  H. Czyżewska-Szafran,et al.  Clonidine action in spontaneously hypertensive rats (SHR) depends on the GABAergic system function , 2005, Amino Acids.

[43]  A. Maqbool,et al.  Increased GABAB Receptor Subtype Expression in the Nucleus of the Solitary Tract of the Spontaneously Hypertensive Rat , 2008, Journal of Molecular Neuroscience.

[44]  D. Haubrich,et al.  Increased susceptibility to seizures and decreased catecholamine turnover in spontaneously hypertensive rats. , 1975, European journal of pharmacology.

[45]  E. Kossoff,et al.  Tourette Syndrome , 2001, Paediatric drugs.

[46]  T. van Groen,et al.  Chronic, severe hypertension does not impair spatial learning and memory in Sprague-Dawley rats. , 2001, Learning & memory.

[47]  A. Arnsten,et al.  Neuronal Mechanisms Underlying Attention Deficit Hyperactivity Disorder , 2008, Annals of the New York Academy of Sciences.

[48]  Y. Ben-Ari,et al.  Kainate, a double agent that generates seizures: two decades of progress , 2000, Trends in Neurosciences.

[49]  K. Starke,et al.  Modulation of neurotransmitter release by presynaptic autoreceptors. , 1989, Physiological reviews.

[50]  V. Monastra Quantitative electroencephalography and attention-deficit/hyperactivity disorder: Implications for clinical practice , 2008, Current psychiatry reports.

[51]  S. Moshé Mechanisms of action of anticonvulsant agents. , 2000, Neurology.

[52]  Rodney J Croft,et al.  Effects of stimulant medications on children with attention-deficit/hyperactivity disorder and excessive beta activity in their EEG , 2003, Clinical Neurophysiology.

[53]  F. Sengpiel,et al.  Apomorphine-induced differences in cortical and striatal EEG and their glutamatergic mediation in 6-hydroxydopamine-treated rats , 2008, Experimental Brain Research.

[54]  V. Vorobyov,et al.  Effects of neurotransmitter agonists on electrocortical activity in the rat kainate model of temporal lobe epilepsy and the modulatory action of basic fibroblast growth factor , 2005, Brain Research.

[55]  W. Barbaresi,et al.  Epilepsy in children with attention-deficit/hyperactivity disorder. , 2010, Pediatric neurology.

[56]  木下 真幸子 Electric cortical stimulation suppresses epileptic and background activities in neocortical epilepsy and mesial temporal lobe epilepsy , 2005 .

[57]  H. Hamoda,et al.  Association between attention-deficit/hyperactivity disorder and epilepsy in pediatric populations , 2009, Expert review of neurotherapeutics.

[58]  G Lallement,et al.  Delta activity as an early indicator for soman-induced brain damage: a review. , 2001, Neurotoxicology.

[59]  R. Barry,et al.  A review of electrophysiology in attention-deficit/hyperactivity disorder: I. Qualitative and quantitative electroencephalography , 2003, Clinical Neurophysiology.

[60]  A. Arnsten,et al.  Neurobiology of Executive Functions: Catecholamine Influences on Prefrontal Cortical Functions , 2004, Biological Psychiatry.

[61]  B. Gaymard,et al.  A Fragile Balance: Perturbation of GABA Mediated Circuit in Prefrontal Cortex Generates High Intraindividual Performance Variability , 2009, PloS one.

[62]  B Stigsby,et al.  Automatic data acquisition and period-amplitude analysis of the electroencephalogram. , 1973, Computer programs in biomedicine.

[63]  E. Basar,et al.  A review of brain oscillations in cognitive disorders and the role of neurotransmitters , 2008, Brain Research.

[64]  Bernice Porjesz,et al.  Genetics of human brain oscillations. , 2006, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[65]  O. Hornykiewicz,et al.  Alpha 2-adrenoceptors modulate kainic acid-induced limbic seizures. , 1985, European journal of pharmacology.

[66]  Timothy Q. Duong,et al.  Quantitative regional cerebral blood flow MRI of animal model of attention-deficit/hyperactivity disorder , 2007, Brain Research.