Preferential modulation of the lateral habenula activity by serotonin-2A rather than -2C receptors: Electrophysiological and neuroanatomical evidence
CNS Neurosci Ther. 2018-02-25; 24(8): 721-733
DOI: 10.1111/cns.12830
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Delicata F(1), Bombardi C(2), Pierucci M(1), Di Maio R(3)(4)(5), De Deurwaerdère P(6), Di Giovanni G(1)(7).
Author information:
(1)Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida, Malta.
(2)Dipartimento di Scienze Mediche Veterinarie, Università di Bologna, Bologna, Italia.
(3)Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA.
(4)Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
(5)Ri.MED Foundation, Palermo, Italy.
(6)Centre National de la Recherche Scientifique (Unité Mixte de Recherche 5287), Bordeaux Cedex, France.
(7)School of Biosciences, Cardiff University, Cardiff, UK.
AIMS: Serotonergic (5-HT) modulation of the lateral habenula (LHb) activity is central in normal and pathologic conditions such as mood disorders. Among the multiple 5-HT receptors (5-HTRs) involved, the 5-HT2C R seems to play a pivotal role. Yet, the role of 5-HT2A Rs in the control of the LHb neuronal activity is completely unknown. METHODS: Single-cell extracellular recording of the LHb neurons was used in rats to study the effect of the general activation and blockade of the 5-HT2C R and 5-HT2A R with Ro 60-0175 and SB242084, TCB-2 and MDL11939, respectively. The expression of both receptors in the LHb 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 LHb recorded neurons, respectively. LHb neurons were either inhibited at low doses or excited at higher doses of the 5-HT2A/C R agonists. SB242084 or MDL11939 (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-HT2C Rs and 5-HT2A Rs are expressed in less than the 20% of the LHb neurons, and they neither colocalize nor make heterodimers. Strikingly, only 5-HT2A Rs are expressed by the majority of LHb astrocyte cells. CONCLUSIONS: Peripheral administration of 5-HT2A R agonist promotes a heterogeneous pattern of neuronal responses in the LHb, and these effects are more prominent than those induced by the 5-HT2C R activation.