N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline studies on the role of 5-HT1A and 5-HT2 receptors in mediating foot-shock-induced ultrasonic vocalisation in adult rats

The role of 5-HT1A and 5-HT2 receptors in mediating foot-shock-induced ultr asonic vocalisation has been studied in rats. Furthermore, behavioural effe cts were correlated to receptor reserves in the brain by means of receptor inactivation with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). Th e dose-dependent inhibition of ultrasonic vocalisation by the 5-HT precurso r, L-5-hydroxy-L-tryptophan (110-450 mu mol/kg), was abolished by pretreatm ent with the 5-HT1A/1B antagonist, (-)-penbutolol (27 mu mol/kg), and the 5 -HT2A/2C antagonist, ritanserin (10 mu mol/kg). The inhibitory actions of t he 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPA T) and the 5-HT2A/5-HT2C agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopro pane (DOI) were reversed by the 5-HT1A antagonist, (N-[2-[4-(2-methoxypheny l)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide (WAY-100 635 ), and the 5-HT2A antagonist, (+/-)alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluo rphenyl)ethyl]-4-piperidine-methanol (MDL 100 151), respectively. Pretreatm ent with EEDQ (24 h, subcutaneous [s.c.]) inhibited foot-shock-induced ultr asonic vocalisation (effective dose(50)=0.95 mu mol/kg) and decreased [H-3] -8-OH-DPAT and [H-3]-ketanserin binding in the brain. Pretreatment with WAY 100 635 (0.3-20 mu mol/kg) 20 min prior to EEDQ administration (1.3 mu mol /kg, s.c.) did not reverse the EEDQ-induced inhibition of ultrasonic vocali sation but protected the 5-HT1A receptors against EEDQ inactivation. Pretre atment with MDL 100 151 (0.83-54 mu mol/kg) 20 min prior to EEDQ administra tion both reversed the EEDQ-induced inhibition of ultrasonic vocalisation a nd protected the 5-HT2A receptors against EEDQ inactivation. These findings demonstrate that 5-HT1A and 5-HT2 receptors are involved in the regulation of ultrasonic vocalisation in rats. However, the function of 5-HT1A and 5- HT2 receptors in this model seems to differ as vocalisation was preserved a fter protection of 5-HT2 but not 5-HT1A recepeors. (C) 1999 Elsevier Scienc e B.V./ECNP. All rights reserved.