Modulation of tianeptine on ion currents induced by inhibitory neurotransmitters in acutely dissociated dorsal raphe neurons of Sprague-Dawley rats.
Classical antidepressant therapy has mainly used selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), but tianeptine appears to possess effects on 5-hydroxytryptamine (5-HT, serotonin) levels in the synaptic cleft contradictory to those of SSRIs. The mechanism behind its antidepressant effects is still unclear. The effect of tianeptine on the electrophysiological characteristics of neurons in the dorsal raphe, where serotonergic neurons mainly originate from, were investigated by the patch-clamp method in the present study. Tianeptine was shown to inhibit the ion currents induced by the inhibitory neurotransmitters GABA and glycine as well as the inwardly rectifying K(+) current induced by 5-HT and 8-hydroxy-2 (di-n-propylamino) tetraline hydrobromide (8-OH-DPAT), a 5-HT(1A) agonist. Tianeptine, however, exerted no effect on the ion current induced by the excitatory neurotransmitter glutamate. These results indicate that tianeptine has an inhibitory effect on ion currents evoked by GABA, glycine, and inwardly rectifying K(+) current induced by 5-HT in the dorsal raphe. This action may increase the excitability of serotonergic neurons of the dorsal raphe.
Kim
Youn-Jung
YJ
Department of Physiology, College of Medicine, Kyung Hee University, #1 Hoigi-dong, Dongdaemoon-gu, 130-701, Seoul, South Korea
Shin
Min-Chul
MC
Kim
Soon-Ae
SA
Chung
Joo-Ho
JH
Kim
Ee-Hwa
EH
Kim
Chang-Ju
CJ
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000494:pharmacology; D005260:Female; D005973:Glutamine / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011903:Raphe Nuclei / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D013841:Thiazepines / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000929:Antidepressive Agents, Tricyclic; D004791:Enzyme Inhibitors; D018846:Excitatory Amino Acids; D015221:Potassium Channels; D012702:Serotonin Antagonists; D013841:Thiazepines; D005973:Glutamine; C050504:tianeptine; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D005033:Ethylmaleimide; D005998:Glycine