215 Mechanisms underlying the sexual inhibitory effect of tramadol; a study in serotonin transporter knockout rats

Abstract

To investigate whether the inhibitory effects of tramadol on sexual behavior are solely due to the blockade of the serotonin (5-HT) transporter (SERT), using SERT knockout rats (SERT-/-). A crossover and randomized design was performed with 36 sexually experienced male Wistar rats (SERT+/+, SERT+/-, SERT-/-; N=12 each). Rats received acute intraperitoneal doses of 0, 5, 10, 20, 40 and 50 mg/kg tramadol hydrochloride. Furthermore, WAY100635 (5-HT1A receptor antagonist) was tested in doses 0, 0.1, 0.3 and 1 mg/kg IP and naloxone hydrochloride (μ-opioid receptor antagonist) in doses 0, 5, 10 and 20 mg/kg, IP. Finally, we tested combinations of vehicle + vehicle, vehicle + tramadol (20 mg/kg), tramadol (20mg/kg) + WAY (0.3 mg/kg), tramadol (20mg/kg) + naloxone (20mg/kg), and tramadol (20mg/kg), + WAY (0.3 mg/kg) + naloxone (20 mg/kg). Experiments were performed over several months on a 30-min sexual behavior test. In all SERT groups, intermediate and high doses of tramadol (20, 40 and 50 mg/kg) significantly decreased ejaculation, mount and intromission frequencies and at the highest dose a total inhibition effect was present. The latencies of ejaculation, mount and intromission were increased which in combination with the decreased frequencies resulted in a decreased efficiency to achieve ejaculation. WAY100635, did not affect sexual behavior in SERT+/+ animals. In accordance with previous findings, sexual behavior was inhibited in SERT-/- animals. Naloxone alone had no effect on sexual behavior, but in combination with WAY100635 or naloxone, tramadol strongly inhibited all sexual behavior parameters. The mixture of tramadol, WAY100635 and naloxone lead to complete elimination of sexual behavior in all groups.