Regarding the HT B receptors they act

Regarding the 5-HT1B receptors, they act as terminal receptors and are involved in the presynaptic regulation of the release of 5-HT. But at spinal level these receptors are principally situated post-synaptically (Sari, 2004). The ability of autoreceptors to regulate extracellular levels of 5-HT during release has made them the focus of much interest. Our results show that SB 216,641, selective 5-HT1B antagonist, modified weakly the antinociceptive effect of paracetamol and CP 93,129, selective 5-HT1B agonist, not produce a clear effect in the antinociceptive effect of paracetamol. In our study, CP 93,129 was used to a doses of 0.125 mg/kg, however, there are studies that show that CP 93,129 at 0.250 mg/kg or 2 mg/kg doses s.c., decreased the antinociceptive effect of paracetamol in the hot plate-test (Roca-Vinardell et al., 2003, Sandrini et al., 2003). Therefore, higher doses of CP 93,129 could have an effect on the antinociceptive effect of paracetamol in the formalin test. Moreover, many data indicate that locomotion may influence nociception, but the changes have not always been well elucidated (Le Bars et al., 2001). In this line, it tetracycline hydrochloride would be interesting to evaluate the spontaneous motor activity after treatment with the drugs used both alone or in combination. As previously mentioned, it is well-known that the descending serotonergic pathway origins at supraspinal sources. The predominant proportion of serotonergic neurons arises from the nucleus raphe magnus, although, a modest sources of serotonergic neurons from dorsal raphe nucleus innervates the spinal cord as well (Wang and Nakai, 1994). Traditionally, actions of 5-HT in the descending serotonergic pathway have been considered to suppressed the nociceptive transmission (Basbaum and Fields, 1978). Nevertheless, opposite actions (pronociceptive or antinociceptive) of 5-HT have been described depending on the 5-HT receptor and localisation of the specific 5-HT receptor types. Thus, activation of the 5-HT1A, 5-HT1B, 5-HT1D and 5-HT7 receptors tends to be antinociceptive, whereas the 5-HT2A and 5-HT3 receptor tend to promote nociception (Rahman et al., 2009, Suzuki et al., 2004). Antinociception in mice produced by rostroventromedial medulla morphine was blocked by spinal 5-HT7 antagonist and hyperalgesia produced by rostroventromedial medulla cholecystokinin was blocked by a spinal 5-HT3 antagonist (Dogrul et al., 2009). In other studies in mice, systemic 5-HT7 agonists blocked hyperalgesia, whereas 5-HT7 antagonists elicited enhanced pain (Brenchat et al., 2009). In this regard, antinociceptive or pronociceptive mechanism can be generated as result of the activation of the descending serotonergic pathway indicating an important serotonergic role for bidirectional pain modulation.