Comparative fos immunoreactivity in the brain after forebrain, brainstem, or combined seizures induced by electroshock, pentylenetetrazol, focally induced and audiogenic seizures in rats

Eells, Jeffrey B.; Clough, Richard W.; Browning, Ronald A.; Jobe, Phillip C.

doi:10.1016/j.neuroscience.2003.08.015

Cited by 93 publications

(65 citation statements)

References 72 publications

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“…Since neuropeptides are typically released under conditions of very high neuronal excitability, NPY and galanin may be preferentially released from LC neurons to prevent severe brainstem seizures under our experimental conditions. In support of this idea, the activation of LC neurons is much greater during brainstem tonic seizures than during forebrain clonic seizures (Eells et al, 2004).…”

Section: Chronic Net Inactivation Has Both Proconvulsant and Anticonvmentioning

confidence: 88%

“…One possibility is that different brain regions are involved. It is generally accepted that forelimb clonic seizures (eg MJ, rearing, and falling seizures) and hindlimb tonic seizures have partially overlapping but distinct anatomical substrates; clonic seizures predominantly activate forebrain regions, while tonic seizures also recruit brainstem structures (Browning, 1994;Eells et al, 2004). The effects of chronic NET blockade on NE signaling may differ between forebrain and brainstem regions.…”

Section: Chronic Net Inactivation Has Both Proconvulsant and Anticonvmentioning

confidence: 99%

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The Effects of Chronic Norepinephrine Transporter Inactivation on Seizure Susceptibility in Mice

Ahern

Javors

Eagles

et al. 2005

Neuropsychopharmacol

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Epilepsy and depression are comorbid disorders, but the mechanisms underlying their relationship have not been identified. Traditionally, many antidepressants have been thought to increase seizure incidence, although this remains controversial, and it is unclear which medications should be used to treat individuals suffering from both epilepsy and depression. Since the neurotransmitter norepinephrine (NE) has both antidepressant and anticonvulsant properties, we speculated that NE transporter (NET) inhibitor antidepressants might be therapeutic candidates for comorbid individuals. To test this idea, we assessed the effects of chronic administration (via osmotic minipump) of the selective NET inhibitor reboxetine on flurothyl-induced seizures in mice. We found that reboxetine had both proconvulsant and anticonvulsant properties; it lowered both seizure threshold and maximal seizure severity. NET knockout (NET KO) mice essentially phenocopied the effects of reboxetine on flurothyl-induced seizures, and the trends were extended to pentylenetetrazole and maximal electroshock seizures (MES). Furthermore, reboxetine had no further effect in NET KO mice, demonstrating the specificity of reboxetine for the NET. We next tested the chronic and acute effects of other classes of antidepressants (desipramine, imipramine, sertraline, bupropion, and venlafaxine) on seizure susceptibility. Only venlafaxine was devoid of proconvulsant activity, and retained some anticonvulsant activity. These results suggest that chronic antidepressant drug treatment has both proconvulsant and anticonvulsant effects, and that venlafaxine is a good candidate for the treatment of epilepsy and depression comorbidity.

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Section: Chronic Net Inactivation Has Both Proconvulsant and Anticonvmentioning

confidence: 88%

Section: Chronic Net Inactivation Has Both Proconvulsant and Anticonvmentioning

confidence: 99%

The Effects of Chronic Norepinephrine Transporter Inactivation on Seizure Susceptibility in Mice

Ahern

Javors

Eagles

et al. 2005

Neuropsychopharmacol

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“…Hindbrain seizure thresholds were assessed by tonic hindlimb extension (THE) seizure activity on PND 34 and 60 (Browning and Nelson, 1985;Eells, et al, 2004). THE seizures begin as tonic forelimb extension, spread to hindlimb flexion, and terminate in full tonic hindlimb extension.…”

Section: Methodsmentioning

confidence: 99%

“…THE seizures begin as tonic forelimb extension, spread to hindlimb flexion, and terminate in full tonic hindlimb extension. Forebrain seizure thresholds were assessed by minimal clonic seizure activity on PND 37 and 63 (Browning and Nelson, 1985;Eells, et al, 2004). Minimal clonic seizures are manifest as rhythmic face and forelimb clonus, rearing and falling, and ventral neck flexion.…”

Section: Methodsmentioning

confidence: 99%

Strain and age affect electroconvulsive seizure testing in rats

2008

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SummaryElectroconvulsive seizure thresholds were compared between adolescent and mature SpragueDawley, Wistar, and Fischer rats. All strains had similar hindbrain or forebrain seizure thresholds as adolescents. As adults, hindbrain or forebrain seizure thresholds were highest for Sprague-Dawley and lowest for Fischer rats. Conversely, limbic seizure thresholds during adolescence were highest for Fischer rats. Additional study is needed to better delineate strain and maturational effects on electroconvulsive seizure testing.

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“…Thus, the drug is highly protective against fully kindled seizures in rodents, but is only weakly effective against MES seizures, which are generated in the brainstem. 327 In addition, tiagabine exacerbates spike-and-wave discharges in some models of absence epilepsy, prossibly due to enhanced action of GABA at GABA B receptors. 328 Acute studies in hippocampal slices show that tiagabine prolongs inhibitory synaptic potentials.…”

Section: Plasma Membrane Gaba Transportersmentioning

confidence: 99%

Molecular Targets for Antiepileptic Drug Development

2007

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Summary:This review considers how recent advances in the physiology of ion channels and other potential molecular targets, in conjunction with new information on the genetics of idiopathic epilepsies, can be applied to the search for improved antiepileptic drugs (AEDs). Marketed AEDs predominantly target voltage-gated cation channels (the ␣ subunits of voltagegated Na ϩ channels and also T-type voltage-gated Ca 2ϩ channels) or influence GABA-mediated inhibition. Recently, ␣2-␦ voltage-gated Ca 2ϩ channel subunits and the SV2A synaptic vesicle protein have been recognized as likely targets. Genetic studies of familial idiopathic epilepsies have identified numerous genes associated with diverse epilepsy syndromes, including genes encoding Na ϩ channels and GABA A receptors, which are known AED targets. A strategy based on genes associated with epilepsy in animal models and humans suggests other potential AED targets, including various voltage-gated Ca 2ϩ channel subunits and auxiliary proteins, A-or M-type voltage-gated K ϩ channels, and ionotropic glutamate receptors. Recent progress in ion channel research brought about by molecular cloning of the channel subunit proteins and studies in epilepsy models suggest additional targets, including G-protein-coupled receptors, such as GABA B and metabotropic glutamate receptors; hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel subunits, responsible for hyperpolarization-activated current I h ; connexins, which make up gap junctions; and neurotransmitter transporters, particularly plasma membrane and vesicular transporters for GABA and glutamate. New information from the structural characterization of ion channels, along with better understanding of ion channel function, may allow for more selective targeting. For example, Na ϩ channels underlying persistent Na ϩ currents or GABA A receptor isoforms responsible for tonic (extrasynaptic) currents represent attractive targets. The growing understanding of the pathophysiology of epilepsy and the structural and functional characterization of the molecular targets provide many opportunities to create improved epilepsy therapies.

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Comparative fos immunoreactivity in the brain after forebrain, brainstem, or combined seizures induced by electroshock, pentylenetetrazol, focally induced and audiogenic seizures in rats

Cited by 93 publications

References 72 publications

The Effects of Chronic Norepinephrine Transporter Inactivation on Seizure Susceptibility in Mice

The Effects of Chronic Norepinephrine Transporter Inactivation on Seizure Susceptibility in Mice

Strain and age affect electroconvulsive seizure testing in rats

Molecular Targets for Antiepileptic Drug Development

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