Fibroblast growth factor 2 (FGF2) modulates the excitability of brain noradrenergic and serotonergic neurons: possible involvement of FGFR1 and FGFR4 receptors.

BACKGROUND

Fibroblast growth factor 2 (FGF2), in addition to its primary function in the connective tissue, plays also a role in the central nervous system (CNS). Thus, anxiolytic, antidepressant, and pro-addictive properties of this molecule have been reported. Our previous study showed that pro-alcohol consumption effect of FGF2 is mediated, at least in part, via its interaction with the central dopaminergic system. The present study aimed to test the hypothesis that pro-addictive and/or antidepressant-like effects of FGF2 can also be linked with FGF2-noradrenaline and FGF2-serotonin (5-HT) interactions.

METHODS

Adult male Wistar rats, weighing 250-350 g, were treated with the recombinant FGF2, selective inhibitors of FGFR1 (PD173074), FGFR2 (lirafugratinib), FGFR4 (BLU9931), or corresponding vehicle. The excitability of the noradrenergic neurons of the locus coeruleus (LC) and serotonergic (5-HT) neurons of the dorsal raphe nucleus (DRN) was assessed using the single-unit in vivo electrophysiology under chloral hydrate anesthesia.

RESULTS

We found that FGF2 stimulated the burst firing of noradrenergic neurons and inhibited the burst firing of 5-HT neurons. PD173074 decreased the density of the spontaneously active noradrenergic neurons in the locus coeruleus, whereas BLU9931 had a stimulatory effect on the burst activity of 5-HT neurons.

CONCLUSION

The psychoactive effects of the FGF2 might be mediated, at least in part, via its interaction with the central monoaminergic circuits. The FGF2-catecholaminergic interactions are putatively mediated via FGFR1, and FGF2-5-HT-crosstalk-via FGFR4. These two receptors can be thus potential targets for the future CNS drugs.