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-HT R seems to play a pivotal role. Yet, the role of 5-HT 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-HT R and 5-HT 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-HT 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-HT Rs and 5-HT Rs are expressed in less than the 20% of the LHb neurons, and they neither colocalize nor make heterodimers. Strikingly, only 5-HT Rs are expressed by the majority of LHb astrocyte cells.
Conclusions: Peripheral administration of 5-HT R agonist promotes a heterogeneous pattern of neuronal responses in the LHb, and these effects are more prominent than those induced by the 5-HT R activation.
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| http://dx.doi.org/10.1111/cns.12830 | DOI Listing |
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