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NLX-112 (a.k.a. F13640 or befiradol), exhibits nanomolar affinity, exceptional selectivity and high agonist efficacy at 5-hydroxytryptamine 5-HT1A receptors. It possesses marked activity in a variety of animal models of depression, pain and L-DOPA-induced dyskinesia. However, its influence on translational biomarkers of central 5-HT1A receptor activation has not been previously described. Here, we report on the activity, in rats, of NLX-112 to increase plasma corticosterone levels and produce hypothermia, two responses which are also elicited by 5-HT1A receptor agonists in humans.NLX-112 elicited dose-dependent hypothermia (minimal effective dose, MED: 0.31 mg/kg p.o.) and also increased plasma corticosterone both by oral and intraperitoneal routes (MED: 0.63 mg/kg in both cases). The increase in corticosterone induced by NLX-112 (0.63 mg/kg p.o.) was abolished by co-administration of the selective 5-HT1A receptor antagonist, WAY100635. Additionally, NLX-112 also dose-dependently induced flat body posture, forepaw treading and lower lip retraction (MEDs 0.31–0.63 mg/kg p.o.).The doses of NLX-112 which induce hypothermia or corticosterone release were similar to those inducing serotonergic behaviors but greater than those reported previously in models of therapeutic-like activity (range 0.04 to 0.16 mg/kg). Overall, the present study provides information for clinical dose estimations of NLX-112 and suggests that therapeutic effects may occur at doses below those at which biomarker responses are observed.NLX-112 (a.k.a. befiradol) is a highly selective serotonin 5-HT1A receptor full agonist.Hypothermia and corticosterone release in rats are 5-HT1A receptor biomarkers.NLX-112 elicits hypothermia and corticosterone release (MED 0.31–0.63 mg/kg i.p.).Active doses of NLX-112 herein are 2 to 16-fold higher than those in therapeutic models.These data are useful for dose extrapolations in the clinical development of NLX-112.