Pharmacological discrimination between effects of carbamazepine on hippocampal basal, Ca2+- and K+-evoked serotonin release

1 To elucidate mechanisms of hippocampal serotonin release and possible mec hanisms of clinical action of carbamazepine (CBZ), we determined interactio n between antagonists of N-type (omega -conotoxin GVIA:GVIA), P-type (omega -agatoxin IVA:IVA) Ca2+ channels, Na+ channel (tetrodotoxin: TTX) and CBZ on hippocampal basal, Ca2+- and K+-evoked serotonin releases, using microdi alysis in freely moving rats. 2 Basal release was reduced by TTX, GVIA and IVA (GVIA>IVA). Ca2+-evoked re lease was reduced by GVIA but unaffected by TTX and IVA. K+-evoked release was reduced by TTX, GVIA and IVA (GVIA < IVA). 3 TTX inhibited actions of IVA and GVIA on respective basal and K+-evoked r eleases, without affecting Ca2+-evoked release. 4 Perfusion with 100 <mu>M CBZ (estimated-concentration in hippocampal tiss ue: 19+/-2 muM) enhanced basal and Ca2+-evoked releases, but reduced K+-evo ked release, whereas 1000 muM CBZ (estimated-concentration in hippocampal t issue: 188+/-16 muM) reduced three types of releases. 5 Under condition of pretreatment with 100 and 1000 muM CBZ, TTX unaffected basal and K+-evoked releases. Under condition of pretreatment with 100 muM CBZ, IVA and GVIA unaffected basal and K+-evoked releases, respectively, b ut GVIA reduced basal, Ca2+-evoked releases and IVA also reduced K+-evoked release. Under condition of pretreatment with 1000 muM CBZ, GVIA unaffected three types of releases, and IVA unaffected basal release but reduced K+-e voked release. 6 These findings contribute towards the possible mechanisms of concentratio n-dependent antiepileptic action of CBZ, which possibly inhibits Na+ channe l related neurotransmitter release mechanisms during K+-evoked stage, and s imultaneously enhances N-type Ca2+ channel related basal serotonin release at the resting stage.