Effect of dihydroergotoxine on the susceptibility of rats to convulsions produced by different convulsant agents

Abstract

The study was undertaken to test further whether diminished GABAergic transmission might be responsible for the increased susceptibility of rats to picrotoxin-induced convulsions. In rats kept individually in cages in a noise-free room, the time between the intraperitoneal injection of the convulsant agent and the onset of convulsions was measured. Acute and subacute treatment with low doses of dihydroergotoxine (0.01-1.0 mg/kg) increased the occurrence and decreased the latency of picrotoxin-induced convulsions. Acute administration of dihydroergotoxine, 1.0 mg/kg, caused convulsions in animals injected with the subconvulsive dose (3 mg/kg) of bicuculline and of 10.0 mg/kg dihydroergotoxine in animals injected with the subconvulsive dose (1.5 mg/kg) of strychnine. Some of the animals injected with the 100% convulsive dose of strychnine were protected by dihydroergotoxine pretreatment (1.0 mg/kg) as evidenced by the lower occurrence of convulsions and fewer animals dying, as well as by a delay in the appearance of convulsions at 10.0 mg/kg. These results together with the previous findings on the GABA system suggest that dihydroergotoxine potentiates the appearance of picrotoxin and bicuculline-induced convulsions by a diminution of GABAergic transmission.

Protective effects of cannabinoid receptor agonists against cocaine and other convulsant-induced toxic behavioural symptoms

“…The doses of cocaine and convulsants were selected based on previous studies (Pericic & Manev 1983 ;Yoshida et al 1987 ;Mares & Velisek 1992 ;Hayase et al 1997 ;Tsuda et al 1997). The final doses used caused convulsive seizures in over 80 % of the mice in a preliminary trial, regardless of lethality and other toxic symptoms : 75 mg kg − 1 for cocaine hydrochloride (Takeda Chemical Industries Ltd, Osaka, Japan), 6 mg kg − 1 for bicuculline (Tocris Cookson Inc., Ballwin, MO), 10 mg kg − 1 for methyl 6,7-dimethoxy-4-ethyl-β-carboline-carboxylate (DMCM ; Sigma-Aldrich, Inc., St Louis, MO), 2 g kg − 1 for -glutamic acid (Nacalai Tesque, Inc., Kyoto, Japan) and 200 mg kg − 1 for Nmethyl--aspartate (NMDA) (Nacalai Tesque, Inc., Kyoto, Japan).…”

Dual species dependent effect of dihydroergosine on the convulsions induced by GABA antagonists

“…We have previously shown (Peri6i6 and Manev, 1983) that another ergot alkaloid dihydroergotoxine affects the incidence and latency of convulsions produced by picrotoxin, a drug that inactivates the GABAA receptor-coupled chloride ion channel (Olsen, 1982), and by bicuculline, a convulsant which appear to act directly to displace bound GABA (Zukin et al, 1974). We have previously shown (Peri6i6 and Manev, 1983) that another ergot alkaloid dihydroergotoxine affects the incidence and latency of convulsions produced by picrotoxin, a drug that inactivates the GABAA receptor-coupled chloride ion channel (Olsen, 1982), and by bicuculline, a convulsant which appear to act directly to displace bound GABA (Zukin et al, 1974).…”

Effect of dihydroergosine (DHESN) on the serotoninergic system and behaviour: Is DHESN a new antidepressive agent?

“…Although these drugs are commonly classified as peripheral c~-adrenoceptor antagonists, they possess agonist and antagonist activities with respect to both central dopamine receptors and ~-adrenoceptors (Goldstein et al 1978;Radulovi6 et al 1984). Dihydrogenated ergot alkaloids also appear to stimulate central 5-HT receptors (Loew et al 1976), they affect GABAergic transmission and potentiate the appearance of picrotoxin-and bicuculline-induced convulsions (Peri~i6 1981a, b;Peri~i6 and Manev 1983). It appears that the actions of ergot drugs on the central nervous system occur with doses lower than those required to produce a significant a-adrenoceptor antagonism in the periphery.…”