PURPOSE: Kindling of audiogenic seizure (AGS) involves >or=14 AGS over 1-2 weeks in genetically epilepsy-prone rats (GEPR-9s) and induces gradual seizure duration increases, epileptiform electroencephalography (EEG), and emergence of post tonic clonus (PTC), which are long-lasting. N-methyl-d-aspartate (NMDA)-receptor activation in lateral amygdala (LA) is implicated in AGS kindling initiation. However, the persistence of AGS kindling appears to be dependent on molecular mechanisms initiated by NMDA-receptor activation, which may involve adenylyl cyclase (AC). This study attempted to mimic AGS kindling persistently in nonkindled GEPR-9s by one-time activation of AC in LA. METHODS: The effects of a single focal bilateral microinjection into LA of an AC activator, MPB forskolin {7-Deacetyl-7-[O-(N-methylpiperazino)-gamma-butyryl]-forskolin dihydrochloride} (25-100 pmol/side), on seizure behavior in GEPR-9s were evaluated. RESULTS: One-time bilateral microinjection of MPB forskolin in GEPR-9s precipitously induced an AGS kindling-like effect, which involved significant increases in seizure duration and long-lasting susceptibility to AGS that culminates in PTC. This effect occurred at 24 h after MPB forskolin microinjection and lasted >or=5 weeks. The effect was seen when AGS was initiated at 1 and 12 h after microinjection, but not if AGS was induced only at 24 h, indicating the importance of the temporal proximity of AGS induction to the MPB forskolin microinjection. DISCUSSION: These findings indicate that one-time activation of AC within the NMDA receptor-mediated molecular cascade results in precipitous induction of AGS kindling. These data further suggest that AC activation in the LA may be an important epileptogenic mechanism that subserves the long-lasting persistence of AGS kindling.
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Tupal et al. (2009) studied this question.