F-15599 (Synonyms: NLX-101)

Animal experiment:

Briefly, in this paradigm, male rats are housed individually in large observation cages (80 × 55 × 50 cm) with an oviduct-ligated female to avoid social isolation and allow sexual behaviour, thereby facilitating territorial behaviour. After 1 week, the baseline level of offensive aggressive behaviour is tested on 3 consecutive days during maximally a 10-min confrontation with an unfamiliar male conspecific (WTG rats). The female partner of the experimental rat is removed from the home observation cage approximately 60 min prior to the start of this social provocation test. Naive male WTG rats, socially housed in groups of 3 in transparent makrolon type IV cages, are used as conspecific intruder animals (average weight 372 ± 9.5 g and 3.5-4 months old). During the first 3 tests, the intruder is removed immediately after the first full attack from the resident and the attack latency time (ALT) is noted. Experimental groups are balanced on the basis of the ALT and the level of offensive behaviour performed during the fourth baseline test (day 4), during which the full range of behaviours is recorded and analysed. Only animals that attacked (i.e. ALT <600 s) are included in the experimental groups. Non-attacking individuals (11 out of 144) are excluded from this study. On the next day (day 5), vehicle (sterile Ultra Pure water, n = 19 and n = 20) or either F15599 (0.0625, 0.125, 0.25, 0.5 and 1.0 mg/kg, IP, experiment 1, n = 45) or F13714 (0.003, 0.006, 0.012, 0.025, 0.062, 0.125, 0.250, IP, experiment 2, n = 50) is administered 30 min before the 10 min confrontation with a drug-free unfamiliar intruder conspecific and their behaviour is recorded again. In addition, in experiment 3, animals are tested 30 min after treatment with either vehicle/vehicle (UP), vehicle/F15599 (0.1 mg/kg) or F13714, WAY-100635 (0.3 mg/kg)/vehicle or WAY100635 (0.3 mg/kg)/ F15599 (0.1 mg/kg) or F13714. Each treatment group consists of 6-8 subjects (n = 41 animals total).

References:

[1]. Meadows SM, et al. Characterizing the differential roles of striatal 5-HT1A auto- and hetero-receptors in the reduction of l-DOPA-induced dyskinesia. Exp Neurol. 2017 Jun;292:168-178.
[2]. de Boer SF, et al. Anti-aggressive effects of the selective high-efficacy 'biased' 5-HT A receptor agonists F15599 and F13714 in male WTG rats. Psychopharmacology (Berl). 2016 Mar;233(6):937-47.
[3]. Lladó-Pelfort L, et al. Preferential in vivo action of F15599, a novel 5-HT(1A) receptor agonist, at postsynaptic 5-HT(1A) receptors. Br J Pharmacol. 2010 Aug;160(8):1929-40.