Dexamethasone and hormones related to the hypothalamic-pituitary-adrenal axis modulate inherited neocortical spindling in DBA/2J mice.
The role of dexamethasone and hormones related to the hypothalamic-pituitary-adrenal (HPA) axis (corticotropin-releasing factor, adrenocorticotropic hormone, corticosterone) in the control of the spike-and-wave spindling episodes (S&W) which can be spontaneously recorded in the electrocorticogram (ECoG) of DBA/2J mice was investigated. Both dexamethasone and hormones related to the HPA axis consistently reduced the S&W in DBA/2J mice. Cycloheximide (a protein synthesis inhibitor) pretreatment significantly delayed the reducing effect of dexamethasone on the S&W in mice. After a transitory decrease, the glucocorticoid receptor antagonist RU-38486 induced a dramatic increase in the rate of the S&W episodes. In addition, mice treated with RU-38486 for 4 days showed a significant increase in the S&W 24 h after the 4th treatment. Our results indicate that dexamethasone as well as hormones related to the HPA axis are able to modulate the S&W in DBA/2J mice, suggesting that this effect may be bound to corticosteroid activity. The time lag (30-60 min) which is necessary for revealing the reducing influence of dexamethasone on the S&W in mice and the influence exerted by cycloheximide on dexamethasone activity support the hypothesis that the effect induced by dexamethasone may be at least in part dependent on genomic mechanisms.
Department of Experimental Pharmacology, University of Naples Federico II, Italy.
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Capasso
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Sorrentino
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Di Giannuario
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Palazzesi
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Pieretti
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Loizzo
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology; D003344:Cortical Synchronization; D003345:Corticosterone / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects*; D004827:Epilepsy / Q000235:genetics / Q000503:physiopathology*; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D006728:Hormones / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D015735:Mifepristone / Q000494:pharmacology; D009044:Motor Cortex / Q000187:drug effects / Q000503:physiopathology; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000502:physiology; D012894:Sleep Stages / Q000187:drug effects / Q000502:physiology; D013003:Somatosensory Cortex / Q000187:drug effects / Q000503:physiopathology; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology
D006728:Hormones; D015735:Mifepristone; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003513:Cycloheximide; D003345:Corticosterone