Selective metabolic activation of the mammillary bodies and their connections during ethosuximide-induced suppression of pentylenetetrazol seizures.

Electroencephalographic (EEG) activity and regional [14C]2-deoxyglucose incorporation in brain were examined in guinea pigs treated with pentylenetetrazol (PTZ), ethosuximide (ESM), phenytoin (PHT), or combinations of these drugs. Convulsant doses of PTZ induced EEG epileptiform discharges in paralyzed and ventilated animals and resulted in a large increase in labeled glucose accumulation in essentially all brain areas. ESM alone depressed EEG activity and accumulation of label, whereas PHT alone had little or no effect. Autoradiographs of PTZ-infused animals pretreated with PHT, which facilitated the onset and increased the severity of the PTZ seizures, were similar to those of animals treated with convulsant alone, with additional label uptake in the globus pallidus and substantia nigra. Pretreatment of PTZ-infused animals with sufficient ESM to prevent most EEG spike activity reduced glucose incorporation in most brain regions, but increased it in some. Selective enhancement of label uptake was observed in the mammillary bodies, mammillothalamic tracts, the anterior nuclei of the thalamus, the mammillary peduncles, and the dorsal and ventral tegmental nuclei of the midbrain. These data suggest that the mammillary nuclei and their projections to the anterior thalamic nucleus and their reciprocal projections to and from the tegmental nuclei may be important in the mediation of seizure activity induced by PTZ and/or the anticonvulsant action of ESM.