Advanced search
1 file | 428.36 KB

Pharmacological and neurochemical characterization of the involvement of hippocampal adrenoreceptor subtypes in the modulation of acute limbic seizures

(2010) JOURNAL OF NEUROCHEMISTRY. 115(6). p.1595-1607
Author
Organization
Abstract
Noradrenaline exerts inhibitory effects on seizure susceptibility. Subtype selective agonists and antagonists were used to identify the anticonvulsant hippocampal adrenoreceptors. Intrahippocampal dialysis was used for administration of all compounds, including pilocarpine for limbic seizure induction, and as the neurotransmitter sampling tool. The noradrenaline reuptake inhibitor maprotiline mediated anticonvulsant effects, associated with dose-dependent increases in extracellular hippocampal noradrenaline, dopamine and GABA levels. At high concentrations, maprotiline produced proconvulsant effects associated with high levels of noradrenaline, dopamine and glutamate. Maprotiline's anticonvulsant effect was blocked by administration of either a selective alpha(2)- and beta(2)-antagonist. alpha(2)-Antagonist administration with maprotiline was associated with a further increase in noradrenaline and dopamine from maprotiline alone; whereas beta(2)-antagonist administered with maprotiline inhibited the dopamine increases produced by maprotiline. alpha(1A)-Antagonism blocked the GABA-ergic but not the anticonvulsive effect of maprotiline. These results were confirmed as combined but not separate alpha(2)- and beta(2)-adrenoreceptor stimulation, using selective agonists, inhibited limbic seizures. Interestingly, alpha(1A)-receptor stimulation and alpha(1D)-antagonism alone also inhibited seizures associated with respectively significant hippocampal GABA increases and glutamate decreases. The main findings of this study are that (i) increased hippocampal noradrenergic neurotransmission inhibits limbic seizures via combined alpha(2)- and beta(2)-receptor activation and (ii) alpha(1A)- and alpha(1D)-adrenoreceptors mediate opposite effects on hippocampal excitability.
Keywords
hippocampus, epilepsy, microdialysis, noradrenaline, EXCITATORY SYNAPTIC-TRANSMISSION, MICROBORE LIQUID-CHROMATOGRAPHY, MESSENGER-RNA EXPRESSION, RAT-BRAIN DEVELOPMENT, ADRENERGIC-RECEPTOR ACTIVATION, INDUCED MOTOR SEIZURES, AMYGDALA-KINDLED RATS, DOPAMINERGIC MODULATION, EXTRACELLULAR GLUTAMATE, ALPHA(2) ADRENOCEPTORS

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 428.36 KB

Citation

Please use this url to cite or link to this publication:

Chicago
Clinckers, Ralph, Tine Zgave, Katia Vermoesen, Alfred Meurs, Yvette Michotte, and Ilse Smolders. 2010. “Pharmacological and Neurochemical Characterization of the Involvement of Hippocampal Adrenoreceptor Subtypes in the Modulation of Acute Limbic Seizures.” Journal of Neurochemistry 115 (6): 1595–1607.
APA
Clinckers, R., Zgave, T., Vermoesen, K., Meurs, A., Michotte, Y., & Smolders, I. (2010). Pharmacological and neurochemical characterization of the involvement of hippocampal adrenoreceptor subtypes in the modulation of acute limbic seizures. JOURNAL OF NEUROCHEMISTRY, 115(6), 1595–1607.
Vancouver
1.
Clinckers R, Zgave T, Vermoesen K, Meurs A, Michotte Y, Smolders I. Pharmacological and neurochemical characterization of the involvement of hippocampal adrenoreceptor subtypes in the modulation of acute limbic seizures. JOURNAL OF NEUROCHEMISTRY. 2010;115(6):1595–607.
MLA
Clinckers, Ralph, Tine Zgave, Katia Vermoesen, et al. “Pharmacological and Neurochemical Characterization of the Involvement of Hippocampal Adrenoreceptor Subtypes in the Modulation of Acute Limbic Seizures.” JOURNAL OF NEUROCHEMISTRY 115.6 (2010): 1595–1607. Print.
@article{7154114,
  abstract     = {Noradrenaline exerts inhibitory effects on seizure susceptibility. Subtype selective agonists and antagonists were used to identify the anticonvulsant hippocampal adrenoreceptors. Intrahippocampal dialysis was used for administration of all compounds, including pilocarpine for limbic seizure induction, and as the neurotransmitter sampling tool. The noradrenaline reuptake inhibitor maprotiline mediated anticonvulsant effects, associated with dose-dependent increases in extracellular hippocampal noradrenaline, dopamine and GABA levels. At high concentrations, maprotiline produced proconvulsant effects associated with high levels of noradrenaline, dopamine and glutamate. Maprotiline's anticonvulsant effect was blocked by administration of either a selective alpha(2)- and beta(2)-antagonist. alpha(2)-Antagonist administration with maprotiline was associated with a further increase in noradrenaline and dopamine from maprotiline alone; whereas beta(2)-antagonist administered with maprotiline inhibited the dopamine increases produced by maprotiline. alpha(1A)-Antagonism blocked the GABA-ergic but not the anticonvulsive effect of maprotiline. These results were confirmed as combined but not separate alpha(2)- and beta(2)-adrenoreceptor stimulation, using selective agonists, inhibited limbic seizures. Interestingly, alpha(1A)-receptor stimulation and alpha(1D)-antagonism alone also inhibited seizures associated with respectively significant hippocampal GABA increases and glutamate decreases. The main findings of this study are that (i) increased hippocampal noradrenergic neurotransmission inhibits limbic seizures via combined alpha(2)- and beta(2)-receptor activation and (ii) alpha(1A)- and alpha(1D)-adrenoreceptors mediate opposite effects on hippocampal excitability.},
  author       = {Clinckers, Ralph and Zgave, Tine and Vermoesen, Katia and Meurs, Alfred and Michotte, Yvette and Smolders, Ilse},
  issn         = {0022-3042},
  journal      = {JOURNAL OF NEUROCHEMISTRY},
  language     = {eng},
  number       = {6},
  pages        = {1595--1607},
  title        = {Pharmacological and neurochemical characterization of the involvement of hippocampal adrenoreceptor subtypes in the modulation of acute limbic seizures},
  url          = {http://dx.doi.org/10.1111/j.1471-4159.2010.07065.x},
  volume       = {115},
  year         = {2010},
}

Altmetric
View in Altmetric
Web of Science
Times cited: