cgs-12066b and 6-chloro-2-(1-piperazinyl)pyrazine

The effects of a number of 5-HT receptor ligands were examined on nonopioid defensive analgesia in male DBA/2 mice. MDL 73005EF (0.05-1.0 mg/kg), a selective 5-HT1A receptor agonist, potently and dose-dependently inhibited the analgesic consequences of social defeat. CGS 12066B (0.5-10.0 mg/kg) and MK-212 (0.3-10.0 mg/kg), selective agonists for 5-HT1B and 5-HT1C sites, respectively, failed to influence this particular form of adaptive pain inhibition. Two 5-HT2/1C receptor antagonists, ritanserin (0.05-10.0 mg/kg) and ICI 169.369 (0.3-10.0 mg/kg), were also devoid of specific effects upon defensive analgesia. Both ritanserin and ICI 169,369 were found to have intrinsic analgetic efficacy and to induce behavioural changes indicative of increased defensiveness. These data, together with previous findings, confirm the specific involvement of 5-HT1A receptor mechanisms in the analgesic consequences of social defeat in male mice. Results are discussed in relation to the role of anxiety in adaptive pain inhibition.

Topics: Aggression; Analgesia; Animals; Dioxins; Dose-Response Relationship, Drug; Male; Mice; Mice, Inbred DBA; Pyrazines; Quinolines; Quinoxalines; Reaction Time; Receptors, Serotonin; Ritanserin; Serotonin Antagonists; Spiro Compounds

Previously, it has been shown that, in small doses, putative 5-HT1A receptor agonists selectively increase ingestion of hypertonic saline without affecting either water or isotonic saline intake. Evidence was obtained in the present series of experiments for selective reduction in hypertonic saline following the administration of a variety of serotonergic directly- and indirectly-acting agonists. Water, isotonic saline (0.9%), or hypertonic saline (1.8%) were made available to separate groups of water-deprived rats. The results indicated some selectivity with the 5-HT-uptake inhibitor and releaser d-fenfluramine and the 5-HT uptake inhibitor fluoxetine, and with the 5-HT agonists mCPP [1-3-chlorophenyl)piperazine] and MK 212 [6-chloro-2-(1-piperazinyl)pyrazine]. In each case, hypertonic intake was significantly suppressed. Distinct from these compounds were TFMPP [1-(3-(trifluoromethyl)phenyl)piperazine], RU 24969 [5-methoxy-3-(1,2,3,6-tetrahydropyridinyl)1H-indole], and quipazine. This second group either reduced fluid intake indiscriminately or reduced water and isotonic saline drinking. Selective reduction in the intake of hypertonic saline did not occur. Finally, peripheral-administration of 5-HT or the 5-HT1B agonist CGS 12066B [7-trifluoromethyl-4(4-methyl-1-piperazinyl-pyrolo) (1,2-a) 1:2 maleate], had no significant effect on fluid intake in any fluid condition. The results are discussed in terms of a possible serotonergic mechanism which may underlie inhibition of hypertonic salt drinking, and which involves mediation through a subtype of the 5-HT1 receptor.

Topics: Animals; Dose-Response Relationship, Drug; Drinking Behavior; Fenfluramine; Fluoxetine; Hypertonic Solutions; Indoles; Male; Piperazines; Pyrazines; Quinoxalines; Quipazine; Rats; Receptors, Serotonin; Serotonin