Open AccessPreferential modulation of the lateral habenula activity by serotonin‐2A rather than ‐2C receptors: Electrophysiological and neuroanatomical evidence
Author(s) -
Delicata Francis,
Bombardi Cristiano,
Pierucci Massimo,
Di Maio Roberto,
De Deurwaerdère Philippe,
Di Giovanni Giuseppe
Publication year - 2018
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12830
Subject(s) - serotonergic , 5 ht receptor , serotonin , receptor , colocalization , electrophysiology , medicine , endocrinology , chemistry , neuroscience , neurotransmitter , premovement neuronal activity , pharmacology , psychology , biology
Abstract Aims Serotonergic (5‐ HT ) modulation of the lateral habenula ( LH b) activity is central in normal and pathologic conditions such as mood disorders. Among the multiple 5‐ HT receptors (5‐ HTR s) involved, the 5‐HT 2C R seems to play a pivotal role. Yet, the role of 5‐HT 2A Rs in the control of the LH b neuronal activity is completely unknown. Methods Single‐cell extracellular recording of the LH b neurons was used in rats to study the effect of the general activation and blockade of the 5‐HT 2C R and 5‐HT 2A R with Ro 60‐0175 and SB 242084, TCB ‐2 and MDL 11939, respectively. The expression of both receptors in the LH b was confirmed using immunohistochemistry. Results Cumulative doses (5‐640 μg/kg, iv) of Ro 60‐0175 and TCB ‐2 affected the activity of 34% and 63% of the LH b recorded neurons, respectively. LH b neurons were either inhibited at low doses or excited at higher doses of the 5‐HT 2A/C R agonists. SB 242084 or MDL 11939 (both at 200 μg/kg, iv) did not modify neuronal firing when injected alone, but reverted the bidirectional effects of Ro 60‐0175 or TCB ‐2, respectively. 5‐HT 2C Rs and 5‐HT 2A Rs are expressed in less than the 20% of the LH b neurons, and they neither colocalize nor make heterodimers. Strikingly, only 5‐HT 2A Rs are expressed by the majority of LH b astrocyte cells. Conclusions Peripheral administration of 5‐HT 2A R agonist promotes a heterogeneous pattern of neuronal responses in the LH b, and these effects are more prominent than those induced by the 5‐HT 2C R activation.