Motor and Electrocorticographic Epileptic Activity Induced by Bicuculline in Developing Rats

Abstract

Motor seizures were induced by intraperitoneally (i.p.) injected bicuculline in 270 rats aged 7, 12, 18, 25, or 90 days. Bicuculline was able to elicit both minimal (clonic) and major (tonic-clonic) seizures in all age groups, but in 7-day-old rats minimal seizures were only noted exceptionally. CD50s (for major seizures) ranged from 2.48 to 2.85 mg/kg in the three younger groups and increased to approximately 7 mg/kg in 25- and 90-day-old rats. An intravenous (i.v.) administration of bicuculline in 67 rats, 18 and 25 days old, caused identical CD50s in these groups, indicating that the difference that occurs with an i.p. administration is due to pharmacokinetic reasons. Electrocorticographic (ECoG) studies in acute experiments as well as in young rats with implanted electrodes demonstrated general principles of the development of EEG: an increase in frequency of individual elements, in generalization of the epileptic activity, in synchronization of activity among various cortical regions, and in the correlation between ECoG and motor phenomena. An exception occurred as an age-related phenomenon: rhythmic activity of the spike-and-wave type. This activity appeared in 18-day-old and older rats and was invariably accompanied by "freezing" of the animals.

Effects of hippocampal high‐frequency electrical stimulation in memory formation and their association with amino acid tissue content and release in normal rats

“…The values for short-term memory formation correspond to the second autoshaping session. In case that animals receiving HFS presented changes in short-term memory formation, another group of rats was manipulated as described above, except that they received a low amount of bicuculline (2 mg/kg, i.p), a well known GABA A receptor antagonist, 5 min before the first autoshaping session in order to block GABA A -induced effects (Zouhar et al, 1989). Immediately after the second session, the animals were killed by decapitation and their brains quickly removed.…”

The benzodiazepine receptor partial agonist Ro 19-8022 suppresses generalized seizures without impairing motor functions in developing rats

“…Therefore, the enhanced incidence of mMS in immature animals cannot be ascribed only to age-related differences of benzodiazepine receptors. There are two possible explanations of this observation: (1) The generator of mMS, localized in the basal forebrain (Browning and Nelson 1986), cannot be triggered by PTZ in 7-and 12-day-old rats, in spite of the fact that it can be reliably set into action by other convulsant drugs like bicuculline (Zouhar et al 1989), isonicotinehydrazide (Mareš and Trojan 1991), 3-mercaptopropionic acid ) and the BZR inverse agonist Ro-4603 (Kubová and Mareš 1994). The pretreatment with various drugs might make it accessible to pentylenetetrazol.…”

Moderate Anticonvulsant Action of Baclofen Does Not Change during Development

“…The difference between the results of intraperitoneal and subcuta neous administration might be explained by a first-pass effect after an intraperitoneal injec tion. The traces of action in 12-dav-old pups in experiment I speak in favor of this explana- tion, because a similar change was described for bicuculline with an abrupt decrease of effect at the end of the 3rd postnatal week in rats [34], A low capacity to metabolize drugs is known also from clinical practice in infants and children [35,36]. In contrast, data con tained in the reference book by Gilman et al [37] speak against this explanation, indicating that baclofen 'is excreted largely unchanged by the kidney'.…”