Age-dependent increase in the threshold for pentylenetetrazole induced maximal seizure in mice

The thresholds for inducing the maximal seizure by pentylenetetrazole (PTZ) were compared for BDFl mice of both sexes with varying ages after intraperitoneal administration of various doses of PTZ. The minimal effective PTZ concentrations (MECs) in the brain for inducing the maximal seizure were significantly higher in 24-month or older mice than in 6-month-old animals of both sexes. Some mice of 30 months did not demonstrate the maximal seizure but died within the 15-min observation period, a phenomenon never observed in mice of 24 months or younger. The relationship between plasma and brain concentrations of PTZ changed little during aging. It was concluded that the brain becomes less sensitive to PTZ with age in regard to its convulsant activity, as was previously shown for electroshock by the authors (1). This observation, coupled with our earlier observations on anticonvulsants (2,3), appears to support the classical hypothesis that age has a dual effect on drug sensitivity i.e. a decrease for stimulants but an increase for sedative (or depressant) drugs.