bemesetron and 1-(3-trifluoromethylphenyl)piperazine

The role of serotonin (5-HT) in the acquisition of the conditioned avoidance response was investigated. The effects of different serotonin agonists and antagonists, administered prior to learning sessions, were studied in groups of naive rats using the two-way shuttle box. Quipazine, an agonist at 5-HT1B/1C/2 receptors, significantly increased avoidance responding in a dose-dependent manner (1.25-10 mg/kg, s.c.). The putative 5-HT1B/1C receptor agonist TFMPP (1-[m-trifluoromethylphenyl] piperazine) at doses of 1.25 and 2.5 mg/kg (s.c.), increased acquisition of conditioned avoidance but showed no significant difference from control at doses of 5 and 10 mg/kg. The 5-HT1A agonist, buspirone, significantly decreased acquisition of conditioned avoidance. Increased acquisition of conditioned avoidance induced by either quipazine or TFMPP was effectively antagonized by the mixed 5-HT 1C/2 receptor antagonists, ketanserin (0.2 and 2 mg/kg, s.c.) and mianserin (1 mg/kg, s.c.). In contrast, spiperone (5-HT1A/2 receptors antagonist: 0.2 mg/kg, s.c.) only inhibited the increased acquisition induced by TFMPP. On the other hand, the 5-HT1A/1B receptors antagonist, pindolol, failed to antagonize the increase in acquisition of conditioned avoidance caused by quipazine or TFMPP. These results suggest that quipazine increases the conditioned avoidance behaviour by an action that might be mediated through stimulation of 5-HT1C receptors. The acquisition of conditioned avoidance induced by TFMPP, which was blocked by ketanserin, mianserin and spiperone but not by pindolol, suggests the involvement of 5-HT1C/2 receptors in the action of TFMPP.

Topics: Animals; Avoidance Learning; Conditioning, Operant; Ketanserin; Male; Mianserin; Nadolol; Pindolol; Piperazines; Prazosin; Quipazine; Rats; Rats, Sprague-Dawley; Receptors, Serotonin; Reference Values; Serotonin Antagonists; Serotonin Receptor Agonists; Spiperone; Tropanes

Our work has focused on identifying the type of serotonin receptor through which serotonin acts as a developmental signal in the central nervous system. Previously, we have found that the regulation of development of ascending serotonergic neurons is through the balance of two serotonin receptors. One, the 5-HT1a receptor, releases a growth factor from astroglial cells. The other receptor is related to a release-regulating autoreceptor and can be stimulated indirectly by serotonin releasers such as fenfluramine. In the present study, we examined the receptors which regulate development of the descending neurons by treating pregnant rats with selective serotonergic drugs, from gestation day 12 until birth. Pups were subsequently tested for alterations in development by nociceptive testing (tail-flick latency) and by determining the binding of 3H-paroxetine, an indicator of serotonin terminal density, in spinal cord. Our results show that agents stimulating the 5-HT1a receptor (8-OH-DPAT) or the 5-HT1b receptor (TFMPP) or substances which release serotonin (fenfluramine) had no effect on the development of spinal serotonergic pathways. However, agents acting on the 5-HT3 receptor did--the agonist phenylbiguanide (PG) increased latency on tail-flick testing (postnatal days 10 and 30), while the antagonist, MDL 72222, decreased latency (postnatal days 10 and 18). Interestingly, both the agonist and the antagonist significantly increased 3H-paroxetine binding on postnatal day 18. Our results are discussed in terms of a possible mechanism by which 5-HT3 receptors may influence development.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Aging; Animals; Biguanides; Female; Fenfluramine; Hypoglycemic Agents; Maternal-Fetal Exchange; Neurons; Pain; Paroxetine; Piperazines; Piperidines; Pregnancy; Rats; Rats, Inbred Strains; Receptors, Serotonin; Serotonin; Serotonin Antagonists; Spinal Cord; Tetrahydronaphthalenes; Tropanes