[Development of tolerance of phenobarbital after administration over several days (author's transl)]

In mice daily testing by maximal electroshock (MES) and pentylenetetrazole infusion (PTZ) 2 h after an i.p. injection of 25 mg/kg penobarbital (PB) was performed on days 1, 2, 4 through 8. The first twitch was delayed as compared to NaCl controls (50.4 +/- 4.8 s; 36.6 +/- 3.6 s; n = 53) on day 2, 4, 6 through 8. There was no tolerance of the PTZ induced tonic extension with Pb-treatment. In contrast, MES-tested mice developed tolerance, at day 5 the number of protected animals fell to about 50%. In view of the constant phenobarbital levels in plasma, a functional tolerance was assumed. The development of tolerance seemed to be connected with the spread of the discharge but not with discharge of the neurones themselves since it was observed only with MES but not wih PTZ-testing.