Supersensitivity to the anticonvulsant and proconvulsant activity of clonidine following noradrenaline depletion induced by 6-hydroxydopamine.
Electrically induced focal cortical seizures were examined in 6-hydroxydopamine (6-OHDA) pretreated or control rats in the presence of 0, 1, 2.5, 5, and 10 micrograms/kg clonidine. In baseline determinations, rats pretreated with 6-OHDA showed lower seizure thresholds and longer behavioral and electrographic seizure than controls. Consistent with other reports, the lowest dose of clonidine (1 microgram/kg) inhibited seizures in control animals; 6-OHDA potentiated the anticonvulsant effect of the lowest dose of clonidine but exacerbated seizure in the presence of the highest dose of clonidine (10 micrograms/kg). Since others have reported proconvulsant effects of clonidine at much higher doses (100 or 1,000 micrograms/kg) using control animals, the depletion of forebrain norepinephrine with 6-OHDA therefore appears to produce a supersensitivity both to the proconvulsant and to the anticonvulsant effect of clonidine. These data suggest that the receptors that mediate the proconvulsant (possibly alpha 1 adrenoceptors) and the anticonvulsant (possibly alpha 2 adrenoceptors) effects are located postsynaptically.
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000502:physiology; D003000:Clonidine / Q000494:pharmacology*; D003292:Convulsants / Q000494:pharmacology*; D004558:Electric Stimulation; D006892:Hydroxydopamines / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000502:physiology*; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains
D000927:Anticonvulsants; D003292:Convulsants; D006892:Hydroxydopamines; D016627:Oxidopamine; D003000:Clonidine; D009638:Norepinephrine