Preferential modulation of the lateral habenula activity by serotonin‐2A rather than ‐2C receptors: Electrophysiological and neuroanatomical evidence

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‐HT2CR seems to play a pivotal role. Yet, the role of 5‐HT2ARs 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‐HT2CR and 5‐HT2AR 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/CR 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‐HT2CRs and 5‐HT2ARs are expressed in less than the 20% of the LHb neurons, and they neither colocalize nor make heterodimers. Strikingly, only 5‐HT2ARs are expressed by the majority of LHb astrocyte cells.

Conclusions

Peripheral administration of 5‐HT2AR agonist promotes a heterogeneous pattern of neuronal responses in the LHb, and these effects are more prominent than those induced by the 5‐HT2CR activation.

Auteurs Bordeaux Neurocampus