In the present study male rat sexual behavior was used to explore the functional properties of FG 5893, a newly developed diphenylbutylpiperazinepyridyl derivative which is a 5-HT1A receptor agonist and a 5-HT1A receptor antagonist. Treatment with FG 5893 (0.1-6.0 mg kg(-1)) stimulated male rat sexual behavior, as evidenced by a decrease in the number of mounts and intromissions to elicit ejaculation, and a shortening of the ejaculation latency. The stimulatory effects varied in a dose-dependent manner, reaching a maximum at 3.0 mg kg(-1). Pretreatment with (+/-)-pindolol (0.5 mg kg(-1) -30 min), a selective 5-HT1A receptor antagonist, completely antagonized the stimulatory effects of FG 5893 (1 mg kg(-1) -20 min) on male sexual behavior. In addition, the behavioral action of FG 5893 was investigated on various components of the 'serotonin behavior syndrome' including flat body posture, forepaw treading, and lower lip retraction. The effects obtained were compared with those induced by treatment with 8-hydroxy-2(di-n-propyl-amino)tetralin (8-OH-DPAT), the prototype of a 5-HT1A receptor agonist. Compared to 8-OH-DPAT, a 100 times higher dose of FG 5893 (10 mg kg(-1)) was needed to elicit flat body posture while forepaw treading was never seen. Lower lip retraction was elicited by the lowest doses of FG 5893 (0.1 mg kg(-1)) and 8-OH-DPAT (0.03 mg kg(-1)). Treatment with (+/-)-pindolol reduced flat body posture elicited by 8-OH-DPAT and completely eradicated the flat body posture induced by FG 5893. The facilitatory effects of FG 5893 on ejaculatory behavior resembled those reported following treatment with typical 5-HT1A receptor agonists and are suggested to be mediated by 5-HT1A receptors. Since FG 5893 was inefficient in stimulating flat body posture, which is suggested to be a postsynaptically mediated syndrome, but readily stimulated lower lip retraction, which is assumed to be a presynaptically mediated behavior syndrome, it is concluded that FG 5893 may act as an agonist presynaptically.
