SK channel blocker apamin attenuates the effect of SSRI fluoxetine upon cell firing in dorsal raphe nucleus: a concomitant electrophysiological and electrochemical in vivo study reveals implications for modulating extracellular 5-HT.
A dual probing methodology was implemented so that combined in vivo voltammetric (electrochemical) and in vivo electrophysiological analysis could be carried out concomitantly in two distinct brain regions of the same anaesthetized animal, i.e., cell body such as the dorsal raphe nucleus (DRN) and related terminal region such as the hippocampus, the frontal cortex, and the amygdala. In particular, this methodology allowed: In addition, the dual probing methodology has been applied to verify the original proposal that a combined treatment with a potassium (SK) channel blocker such as apamin and an SSRI (i.e., fluoxetine) could overcome the slow onset of the SSRI upon central 5-HT activity that could be related to the slow onset of its therapeutic action. Briefly, the effect of apamin either alone or followed by fluoxetine upon cell firing in the DRN (in vivo electrophysiology) and concomitantly upon 5-HT levels (in vivo voltammetry) in the amygdala (forebrain structure involved in mood regulation and innervated by ascending 5-HT projections from the DRN) was studied.
Crespi
Francesco
F
Biology Dept, Neurosciences CEDD GlaxoSmithKline, Medicines Research Centre, via A. Fleming 4, 37135 Verona, Italy. francesco.m.crespi@gsk.com
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects*; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001030:Apamin / Q000494:pharmacology*; D004333:Drug Administration Routes; D004347:Drug Interactions; D004563:Electrochemistry / Q000379:methods; D004594:Electrophysiology / Q000379:methods; D005473:Fluoxetine / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013997:Time Factors
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D001030:Apamin; D005473:Fluoxetine; D026902:Potassium Channel Blockers; D012701:Serotonin; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors