The effect of age on the adaptation of the brain to the anticonvulsant effect of phenobarbital in mice.

The anticonvulsant effect of phenobarbital was examined in young (6 month old) and old (24 month old) BDF1 female mice consisting of three groups each (one control and two chronically dosed phenobarbital groups), using the abolition of the tonic hindlimb extensor component of maximal electroshock seizure as the index. The minimal effective concentrations (MEC) of phenobarbital in plasma and brain in old control mice that were given a vehicle (tragacanth) for one week were significantly lower in comparison to the respective values in young adult control mice with the same treatment, confirming our previous findings. In young mice chronically treated with phenobarbital for one week (20 mg/kg daily for two days followed by daily dose of 50 mg/kg for 5 days), the MECs in both plasma and brain were significantly higher compared with respective control values. The 3 week treatment also produced an increase in MEc comparable to the one-week treatment. The same one-week treatment with phenobarbital in old mice similarly caused significantly higher plasma and brain MEC values but 3-week-treatment values were not significantly different from corresponding control values. It is concluded that the development of brain adaptation to phenobarbital is almost equal for young and old mice, so that the reduction in MEC with age indicates the need for lowered dosages for the aged, even when the age effect on brain adaptation developed to chronic dosing is taken into consideration.