Electroencephalographic and Behavioral Effects of a GABA Agonist (Muscimol) on Photosensitive Epilepsy in the Baboon, Papio papio

Abstract

Muscimol, 0.25-1.0 mg/kg, i.v., was administered acutely to 4 adolescent baboons, Papio papio, that show photically induced epilepsy. On the EEG, slowing of background rhythms was associated with the appearance of spikes, polyspikes, and recurring symmetrical spike-wave complexes. These changes were maximal 0.5-2 hr after muscimol injection. Regular testing with intermittent light stimulation showed either no change from control responses or a more severe epileptiform EEG 0.1-3 hr after muscimol. Photically induced myoclonus was not modified by muscimol. Despite its GABA-abonist properties, muscimol is not an effective anticonvulsant.

Alteration of behavior in mice by muscimol is associated with regional electroencephalogram synchronization

“…Taken together, it seems that the sedative effects of GABA A agonists and GABA A modulators are related to an increased global synchrony of cortical neuronal activity. These results are consistent with the increased EEG power in the slow-wave range, high-amplitude synchronous EEG waves or spikes observed in the rat (Peeters et al, 1989, Lancel et al, 1996, Lancel et al, 1997, in cats (Fariello et al, 1981), and in baboon Papio papio (Pedley et al, 1979).…”

“…These findings are consistent with EEG alterations found in an absence epilepsy-prone rat strain (WAG\Rij), where icv muscimol induced a dose-dependent abnormal EEG pattern consisting of slow waves and spikes which persisted for several hours (Peeters et al, 1989). Bilaterally synchronous spikewaves appeared after systemic administration of muscimol in the cat (Fariello et al, 1981), while in the baboon Papio papio, muscimol induced spike-wave complexes (Pedley et al, 1979) similar to the EEG changes elicited by 5 mg/kg muscimol in patients suffering from Huntington's disease (Shoulson et al, 1978). Other behavioral effects of muscimol were prolongation of propofol-induced anesthesia in mice (Irifune et al, 2003), and a dose-dependent increase in the duration of spontaneous petit mal-like seizures in the rat (Vergnes et al, 1984).…”

Drugs That Increase Γ‐aminobutyric Acid Transmission Protect Against the High Pressure Neurological Syndrome

“…or 600 ng i.c.v. Excitant effects of muscimol have been described previousl) (Pedley, Horton & Meldrum, 1979) and these are thought not to be due to its GABA agonist activit) (Menon & Vivonia, 1981a, b). Convulsant actions have also been reported with high doses of AOAA and DABA.…”

GABAergic mechanisms in the pathogenesis and treatment of epilepsy.

“…However they are proconvulsant in Wistar rats with spontaneous petit-mal-like epilepsy (Vergnes et al, 1984). They also enhance spike and wave discharges and induce diffuse myoclonus in baboons with photosensitive epilepsy (Pedley et al, 1979;Meldrum & Horton, 1980). L-baclofen, the GABAB agonist, likewise appears anticonvulsant in some rodent tests but facilitates spike and wave discharges both in Wistar rats and in photosensitive baboons (Meldrum & Horton, 1974).…”