Repeated administration of subconvulsant doses of GABA antagonist drugs

Abstract

Repeated subconvulsant doses of the GABA antagonist drugs picrotoxin (5 mg/kg), pentylenetetrazol (PTZ) (30 mg/kg), and bicuculline (3.5 mg/kg), were given IP once daily to rats. Picrotoxin produced rapid kindling to full seizures in about 5 days, PTZ produced sporadic myoclonic seizures after 17 days, PTZ produced sporadic myoclonic seizures after 17 days whereas bicuculline only produced occasional mild jerking. Following these treatments, seizure thresholds to these drugs were measured by an IV infusion method to minimise problems of systemic uptake and metabolism of the drugs. Picrotoxin- and PTZ-treated animals showed no alteration in seizure threshold. However, following bicuculline pretreatment, seizure threshold was raised. Methodological problems in the interpretation of pharmacological kindling are discussed.

An Experimental Set-Up for Measurement of the Power Absorbed From 900 MHZ GSM Standing Waves by Small Animals, Illustrated by Application to Picrotoxin-Treated Rats

“…The effect of radiation on c-Fos-positive cell counts in picrotoxin-treated rats is coherent with convulsions having been suffered by the irradiated rats (group PR) but not by the non-irradiated rats (group PNR); both findings suggest that 2 hours' exposure to 1 W GSM radiation markedly increased uncontrolled neuronal activity in the GABAergic and/or glutamatergic systems involving the frontal motor and piriform cortex [13,22] following sensitization of these systems by subconvulsive doses of picrotoxin [14]. Despite of the fact that the experiments were Table 1.…”

“…Group PR animals were destined for injection of picrotoxin followed by 2 hours' exposure in the radiation chamber to 900 MHz GSM-type radiation, i.e., radiation pulsed with a TDM period of 4615 µs and a slot width of 577 µs; group PNR for injection of picrotoxin followed by 2 hours' immobilization in the radiation chamber without radiation; group CR for 2 hours' exposure to radiation without prior injection of picrotoxin; and group CNR for 2 hours' immobilization in the chamber without radiation or prior injection of picrotoxin. Picrotoxin, when used, was injected intraperitoneally at the subconvulsive dosage of 2 mg Kg −1 [13,14]. In all groups, the animals were used one at a time, and the receiving antenna and video camera were present in the chamber in all experiments.…”

“…In previous work [13], we have in fact shown that radiation of the type used by the Global System for Mobile communications (GSM) triggers seizures in rats in which a seizure-prone state analogous to epilepsy had been induced by subconvulsive doses of picrotoxin [14].…”

ABHD6 Blockade Exerts Antiepileptic Activity in PTZ-Induced Seizures and in Spontaneous Seizures in R6/2 Mice

“…Using a dose of 1 mg/kg picrotoxin, below the dose range (>5mg/kg) required to produce seizures on a single dosing (Nutt et al, 1982), animals were treated with WWL123 or vehicle (4 hours prior to receiving PTZ), and then with picrotoxin (1 mg/kg, i.p.) or vehicle (5 minutes prior to receiving PTZ).…”

Acute Effects of a Bicyclophosphate Neuroconvulsant on Monoamine Neurotransmitter and Metabolite Levels in the Rat Brain

“…These changes in monoamine Note. repeated exposure to subconvulsive doses of some GABAergic convulsants can result in chemical kindling of generalized motor seizures (Nutt et al, 1982;Ono et al, 1990), there has been little investigation of the modulation of non-GABA neurotransmitter systems by subconvulsive versus convulsive dose administrations of GABAergic convulsants. N refers to the number of occurrences of the specified seizure type at a given dose.…”