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.
Capasso
A
A
Department of Experimental Pharmacology, University of Naples Federico II, Italy.
Sorrentino
L
L
Di Giannuario
A
A
Palazzesi
S
S
Pieretti
S
S
Loizzo
A
A
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