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Adrenergic receptor modulation of hippocampal CA3 network activity.
- Source :
-
Epilepsy research [Epilepsy Res] 2005 Aug-Sep; Vol. 66 (1-3), pp. 117-28. - Publication Year :
- 2005
-
Abstract
- Norepinephrine (NE) has demonstrated proconvulsant and antiepileptic properties; however, the specific pharmacology of these actions has not been clearly established. To address this, we studied the effect of NE on hippocampal CA3 epileptiform activity. Frequency changes of burst discharges in response to NE were biphasic; low concentrations increased the number of bursts, while higher concentrations reduced their frequency, suggesting the involvement of multiple adrenergic receptor (AR) types. This hypothesis was confirmed when, in the presence of betaAR blockade, increasing concentrations of NE caused a monophasic decrease in epileptiform activity. Antagonists selective for alpha1 or alpha2ARs were then used to determine which alphaAR type was involved. While discriminating concentrations of the alpha1AR antagonists prazosin and terazosin had no effect, selective amounts of the alpha2AR antagonists RS79948 and RX821002 significantly reduced the potency of NE in decreasing epileptiform activity. Furthermore, this antiepileptic action of NE persisted when all GABA-mediated inhibition was blocked. This data suggests that, under conditions of impaired GABAergic inhibition, the excitatory and inhibitory effects of NE on hippocampal CA3 epileptiform activity are mediated primarily via beta and alpha2ARs, respectively. Moreover, our results imply that the antiepileptic effect of alpha2AR activation in CA3 is not dependent on the GABAergic system.
- Subjects :
- Action Potentials drug effects
Action Potentials physiology
Adrenergic alpha-Antagonists pharmacology
Adrenergic beta-Antagonists pharmacology
Animals
Animals, Newborn
Behavior, Animal
Bicuculline
Dose-Response Relationship, Drug
Drug Interactions
Epilepsy chemically induced
Epilepsy physiopathology
GABA Antagonists pharmacology
Hippocampus drug effects
In Vitro Techniques
Nerve Net drug effects
Neural Inhibition drug effects
Neural Inhibition physiology
Norepinephrine pharmacology
Phentolamine pharmacology
Phosphinic Acids pharmacology
Pindolol pharmacology
Propanolamines pharmacology
Rats
Rats, Sprague-Dawley
Hippocampus physiopathology
Nerve Net physiopathology
Receptors, Adrenergic physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0920-1211
- Volume :
- 66
- Issue :
- 1-3
- Database :
- MEDLINE
- Journal :
- Epilepsy research
- Publication Type :
- Academic Journal
- Accession number :
- 16140503
- Full Text :
- https://doi.org/10.1016/j.eplepsyres.2005.07.007