Aconitine induces prolonged seizure-like events in rat neocortical brain slices.
Aconitine effects on the hippocampal slice preparation have been well documented and include acute inhibitory and prolonged excitatory effects. To date, the effect of aconitine on neocortical activity has not been investigated. The aim of this study was to characterise the acute and long term effects of aconitine on cortical local field potential activity. Neocortical slices from juvenile Sprague-Dawley rats were perfused at room temperature with aconitine in normal artificial cerebrospinal fluid (aCSF) (n=10). Spontaneous local field potential activity was recorded from the somatosensory cortex. The calcium dependence of aconitine-induced activity was investigated using low-calcium aCSF (n=8). To isolate sodium and N-methyl-d-aspartate (NMDA) channel effects, phenytoin (n=4) and 2-amino-5-phosphono-pentanoic acid (APV) (n=6) were co-administered with aconitine, respectively. Aconitine consistently induced a dramatic increase in population "spike" activity after prolonged (89.5+/-36.6 min) application in normal aCSF. This activity surge was eliminated in low-calcium aCSF and when aconitine was co-administered with phenytoin and APV. The acute effects of aconitine application were variable and included an increase in the frequency of population spikes, appearance of oscillatory seizure-like activity and prolonged bursts of multiunit activity. No acute inhibitory effects were observed. Aconitine has acute and prolonged excitatory effects on neocortical activity. The latter is effected by calcium-dependent mechanisms, in keeping with known effects of aconitine on hippocampal slices. Both sodium and NMDA channels are involved in mediating the calcium-dependent aconitine effects.
Voss
Logan J
LJ
Department of Anaesthesia, Waikato Hospital, Hamilton, New Zealand. VossL@waikatodhb.govt.nz
Voss
Janet M
JM
McLeay
Lance
L
Sleigh
James W
JW
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000157:Aconitine / Q000633:toxicity*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002491:Central Nervous System Agents / Q000633:toxicity*; D002555:Cerebrospinal Fluid / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D019579:Neocortex / Q000187:drug effects* / Q000378:metabolism; D010672:Phenytoin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D013003:Somatosensory Cortex / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D002491:Central Nervous System Agents; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D010672:Phenytoin; D015763:2-Amino-5-phosphonovalerate; D002118:Calcium; D000157:Aconitine