5-HT(1A)-MEDIATED LOWER LIP RETRACTION - EFFECTS OF 5-HT(1A) AGONISTS AND ANTAGONISTS

This study investigated the production of lower lip retraction (LLR) in the rat by the 5-hydroxytryptamine1A (5-HT1A) agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) and the effect of the putative 5-HT1A antagonists pindolol and (1-(2-methoxy-phenyl)-4-[4-(2-phthalimido)-butyl]-piperazine (NAN190). 8-OH-DPAT (0.125-1.0 mg/kg, IP) caused a dose-related increase in LLR. Pindolol (10-40 mg/kg, IP) and NAN190 (2.5-10 mg/kg, IP) produced a dose-related block of 8-OH-DPAT-induced LLR. Pindolol (10-40 mg/kg, IP) when administered alone was also found to cause LLR, suggesting that pindolol behaves as a partial agonist in this model. This was not the case with NAN 190 (2.5- 10 mg/kg, IP), which failed to produce LLR; however, NAN190 (2.5-10 mg/kg, IP) produced a dose-related block of the pindolol-induced LLR. These results clearly demonstrate that the LLR model can be used to detect 5-HT1A agonists, partial agonists, and antagonists.