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

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Abstract
To elucidate mechanisms of hippocampal serotonin release and possible mechanisms of clinical action of carbamazepine (CBZ), we determined interaction between antagonists of N‐type (ω‐conotoxin GVIA:GVIA), P‐type (ω‐agatoxin IVA:IVA) Ca2+ channels, Na+ channel (tetrodotoxin: TTX) and CBZ on hippocampal basal, Ca2+‐ and K+‐evoked serotonin releases, using microdialysis in freely moving rats. Basal release was reduced by TTX, GVIA and IVA (GVIA>IVA). Ca2+‐evoked release was reduced by GVIA but unaffected by TTX and IVA. K+‐evoked release was reduced by TTX, GVIA and IVA (GVIA+‐evoked releases, without affecting Ca2+‐evoked release. Perfusion with 100 μM CBZ (estimated‐concentration in hippocampal tissue: 19±2 μM) enhanced basal and Ca2+‐evoked releases, but reduced K+‐evoked release, whereas 1000 μM CBZ (estimated‐concentration in hippocampal tissue: 188±16 μM) reduced three types of releases. Under condition of pretreatment with 100 and 1000 μM CBZ, TTX unaffected basal and K+‐evoked releases. Under condition of pretreatment with 100 μM CBZ, IVA and GVIA unaffected basal and K+‐evoked releases, respectively, but GVIA reduced basal, Ca2+‐evoked releases and IVA also reduced K+‐evoked release. Under condition of pretreatment with 1000 μM CBZ, GVIA unaffected three types of releases, and IVA unaffected basal release but reduced K+‐evoked release. These findings contribute towards the possible mechanisms of concentration‐dependent antiepileptic action of CBZ, which possibly inhibits Na+ channel related neurotransmitter release mechanisms during K+‐evoked stage, and simultaneously enhances N‐type Ca2+ channel related basal serotonin release at the resting stage. British Journal of Pharmacology (2001) 133, 557–567; doi:10.1038/sj.bjp.0704104

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