title: Serotonin stimulates lateral habenula via activation of the post-synaptic serotonin 2/3 receptors and transient receptor potential channels.
abstract: There is growing interest on the role of the lateral habenula (LHb) in depression, because it closely and bilaterally connects with the serotoninergic raphe nuclei. The LHb sends glutamate efferents to the raphe nuclei, while it receives serotoninergic afferents, and expresses a high density of serotonin (5-HT) receptors. Recent studies suggest that 5-HT receptors exist both in the presynaptic and postsynaptic sites of LHb neurons, and activation of these receptors may have different effects on the activity of LHb neurons. The current study focused on the effect of 5-HT on the postsynaptic membrane. We found that 5-HT initiated a depolarizing inward current (I((5-HTi))) and accelerated spontaneous firing in ∼80% of LHb neurons in rat brain slices. I((5-HTi)) was also induced by the 5-HT uptake blocker citalopram, indicating activity of endogenous 5-HT. I((5-HTi)) was diminished by 5-HT(2/3) receptor antagonists (ritanserin, SB-200646 or ondansetron), and activated by the selective 5-HT(2/3) agonists 1-(3-Chlorophenyl) piperazine hydrochloride or 1-(3-Chlorophenyl) biguanide hydrochloride. Furthermore, I((5-HTi)) was attenuated by 2-Aminoethyl diphenylborinate, a blocker of transient receptor potential channels, and an IP3 receptor inhibitor, indicating the involvement of transient receptor potential channels. These results demonstrate that the reciprocal connection between the LHb and the 5-HT system highlights a key role for 5-HT stimulation of LHb neurons that may be important in the pathogenesis of depression.
authors.affiliation: Department of Anesthesiology, Pharmacology and Physiology, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, NJ, USA.
authors.forename: Wanhong
authors.initials: W
authors.lastname: Zuo
authors.affiliation: Department of Anesthesiology, Pharmacology and Physiology, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, NJ, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Pharmacology and Physiology, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, NJ, USA.
authors.forename: Guiqin
authors.initials: G
authors.lastname: Xie
authors.affiliation: Department of Anesthesiology, Pharmacology and Physiology, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, NJ, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Gregor
authors.affiliation: Department of Anesthesiology, Pharmacology and Physiology, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, NJ, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Bekker
authors.affiliation: Department of Anesthesiology, Pharmacology and Physiology, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, NJ, USA. Electronic address: ye@njms.rutgers.edu.
authors.forename: Jiang-Hong
authors.initials: JH
authors.lastname: Ye
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D004338:Drug Combinations; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D005260:Female; D019262:Habenula / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D018377:Neurotransmitter Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology*; D018490:Serotonin Agents / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D050051:Transient Receptor Potential Channels / Q000378:metabolism*
chemical_list: D004338:Drug Combinations; D018683:Excitatory Amino Acid Agents; D018377:Neurotransmitter Agents; D044348:Receptors, Serotonin, 5-HT2; D044406:Receptors, Serotonin, 5-HT3; D018490:Serotonin Agents; D026941:Sodium Channel Blockers; D050051:Transient Receptor Potential Channels; D012701:Serotonin; D013779:Tetrodotoxin
keywords: Depression; Dorsal raphe nuclei; Inward current; Lateral habenula; Serotonin receptors