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. 1990 Nov;101(3):667–673. doi: 10.1111/j.1476-5381.1990.tb14138.x

Behavioural evidence for functional interactions between 5-HT-receptor subtypes in rats and mice.

H H Berendsen 1, C L Broekkamp 1
PMCID: PMC1917735  PMID: 2150180

Abstract

1. Different 5-hydroxytryptamine (5-HT) receptor subtypes mediate different behavioural responses. Compounds acting at more than one 5-HT receptor exert behavioural effects which may be the result of response competition or a specific interaction between pathways within the CNS. Therefore the mutual interaction between different 5-HT receptor subtypes was studied. 2. Hypothermia and hypoactivity in mice induced by the 5-HT1A-agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) could be attenuated by the preferential 5-HT1C-agonists MK 212, 1-(meta-chlorophenyl)-piperazine (mCPP) and m-trifluoromethyl phenyl piperazine (TFMPP), and by the mixed 5-HT2/1C-agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). The mixed 5-HT1A/1B-agonist CGS 12066B at 10 mg kg-1 potentiated hypothermia and had no effect on hypoactivity. 3. Forepaw treading in rats induced by the 5-HT1A-agonist 8-OH-DPAT was attenuated by the 5-HT1C-agonists MK 212 and mCPP. The 5-HT1C-agonist TFMPP had a bimodal effect: at low doses (less than 1 mg kg-1) it potentiated, and at higher doses (greater than 2.2 mg kg-1) it attenuated forepaw treading, the mixed 5-HT2/1C-agonist DOI produced 5-HT2-related behaviours and potentiated 8-OH-DPAT-induced forepaw treading. This indicates an attenuating effect of 5-HT1C-receptor activation and a potentiating effect of 5-HT2-receptor activation. CGS 12066B had no effect in this respect. 4. Head shakes in rats induced by DOI could be attenuated by 8-OH-DPAT, TFMPP, mCPP and MK 212. The ID50S were 0.03, 0.7, 0.1 and .2 mg kg-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Arnt J., Hyttel J. Facilitation of 8-OHDPAT-induced forepaw treading of rats by the 5-HT2 agonist DOI. Eur J Pharmacol. 1989 Feb 14;161(1):45–51. doi: 10.1016/0014-2999(89)90178-7. [DOI] [PubMed] [Google Scholar]
  2. Berendsen H. H., Jenck F., Broekkamp C. L. Involvement of 5-HT1C-receptors in drug-induced penile erections in rats. Psychopharmacology (Berl) 1990;101(1):57–61. doi: 10.1007/BF02253718. [DOI] [PubMed] [Google Scholar]
  3. Berendsen H. H., Jenck F., Broekkamp C. L. Selective activation of 5HT1A receptors induces lower lip retraction in the rat. Pharmacol Biochem Behav. 1989 Aug;33(4):821–827. doi: 10.1016/0091-3057(89)90477-2. [DOI] [PubMed] [Google Scholar]
  4. Broekkamp C. L., Berendsen H. H., Jenck F., Van Delft A. M. Animal models for anxiety and response to serotonergic drugs. Psychopathology. 1989;22 (Suppl 1):2–12. doi: 10.1159/000284620. [DOI] [PubMed] [Google Scholar]
  5. Cohen M. L., Fuller R. W. Antagonism of vascular serotonin receptors by m-chlorophenylpiperazine and m-trifluoromethylphenylpiperazine. Life Sci. 1983 Feb 14;32(7):711–718. doi: 10.1016/0024-3205(83)90303-x. [DOI] [PubMed] [Google Scholar]
  6. Conn P. J., Sanders-Bush E. Relative efficacies of piperazines at the phosphoinositide hydrolysis-linked serotonergic (5-HT-2 and 5-HT-1c) receptors. J Pharmacol Exp Ther. 1987 Aug;242(2):552–557. [PubMed] [Google Scholar]
  7. Davis M., Cassella J. V., Wrean W. H., Kehne J. H. Serotonin receptor subtype agonists: differential effects on sensorimotor reactivity measured with acoustic startle. Psychopharmacol Bull. 1986;22(3):837–843. [PubMed] [Google Scholar]
  8. Goodwin G. M., De Souza R. J., Green A. R., Heal D. J. The pharmacology of the behavioural and hypothermic responses of rats to 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Psychopharmacology (Berl) 1987;91(4):506–511. doi: 10.1007/BF00216019. [DOI] [PubMed] [Google Scholar]
  9. Goodwin G. M., De Souza R. J., Green A. R. The pharmacology of the hypothermic response in mice to 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). A model of presynaptic 5-HT1 function. Neuropharmacology. 1985 Dec;24(12):1187–1194. doi: 10.1016/0028-3908(85)90153-4. [DOI] [PubMed] [Google Scholar]
  10. Goodwin G. M., Green A. R. A behavioural and biochemical study in mice and rats of putative selective agonists and antagonists for 5-HT1 and 5-HT2 receptors. Br J Pharmacol. 1985 Mar;84(3):743–753. doi: 10.1111/j.1476-5381.1985.tb16157.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Grahame-Smith D. G. Studies in vivo on the relationship between brain tryptophan, brain 5-HT synthesis and hyperactivity in rats treated with a monoamine oxidase inhibitor and L-tryptophan. J Neurochem. 1971 Jun;18(6):1053–1066. doi: 10.1111/j.1471-4159.1971.tb12034.x. [DOI] [PubMed] [Google Scholar]
  12. Gudelsky G. A., Koenig J. I., Meltzer H. Y. Thermoregulatory responses to serotonin (5-HT) receptor stimulation in the rat. Evidence for opposing roles of 5-HT2 and 5-HT1A receptors. Neuropharmacology. 1986 Dec;25(12):1307–1313. doi: 10.1016/0028-3908(86)90101-2. [DOI] [PubMed] [Google Scholar]
  13. HESS S. M., DOEPFNER W. Behavioral effects and brain amine content in rats. Arch Int Pharmacodyn Ther. 1961 Nov 1;134:89–99. [PubMed] [Google Scholar]
  14. Hillegaart V., Wadenberg M. L., Ahlenius S. Effects of 8-OH-DPAT on motor activity in the rat. Pharmacol Biochem Behav. 1989 Mar;32(3):797–800. doi: 10.1016/0091-3057(89)90036-1. [DOI] [PubMed] [Google Scholar]
  15. Hjorth S. Hypothermia in the rat induced by the potent serotoninergic agent 8-OH-DPAT. J Neural Transm. 1985;61(1-2):131–135. doi: 10.1007/BF01253058. [DOI] [PubMed] [Google Scholar]
  16. Hoyer D. Functional correlates of serotonin 5-HT1 recognition sites. J Recept Res. 1988;8(1-4):59–81. doi: 10.3109/10799898809048978. [DOI] [PubMed] [Google Scholar]
  17. Hoyer D. Molecular pharmacology and biology of 5-HT1C receptors. Trends Pharmacol Sci. 1988 Mar;9(3):89–94. doi: 10.1016/0165-6147(88)90174-5. [DOI] [PubMed] [Google Scholar]
  18. Jenck F., Broekkamp C. L., Van Delft A. M. Opposite control mediated by central 5-HT1A and non-5-HT1A (5-HT1B or 5-HT1C) receptors on periaqueductal gray aversion. Eur J Pharmacol. 1989 Feb 28;161(2-3):219–221. doi: 10.1016/0014-2999(89)90847-9. [DOI] [PubMed] [Google Scholar]
  19. Maj J., Lewandowska A. Central serotoninmimetic action of phenylpiperazines. Pol J Pharmacol Pharm. 1980 Jul-Aug;32(4):495–504. [PubMed] [Google Scholar]
  20. Neale R. F., Fallon S. L., Boyar W. C., Wasley J. W., Martin L. L., Stone G. A., Glaeser B. S., Sinton C. M., Williams M. Biochemical and pharmacological characterization of CGS 12066B, a selective serotonin-1B agonist. Eur J Pharmacol. 1987 Apr 7;136(1):1–9. doi: 10.1016/0014-2999(87)90772-2. [DOI] [PubMed] [Google Scholar]
  21. Pawłowski L. Amitriptyline and femoxetine, but not clomipramine or citalopram, antagonize hyperthermia induced by directly acting 5-hydroxytryptamine-like drugs in heat adapted rats. J Pharm Pharmacol. 1984 Mar;36(3):197–199. doi: 10.1111/j.2042-7158.1984.tb06940.x. [DOI] [PubMed] [Google Scholar]
  22. Schoeffter P., Hoyer D. Interaction of arylpiperazines with 5-HT1A, 5-HT1B, 5-HT1C and 5-HT1D receptors: do discriminatory 5-HT1B receptor ligands exist? Naunyn Schmiedebergs Arch Pharmacol. 1989 Jun;339(6):675–683. doi: 10.1007/BF00168661. [DOI] [PubMed] [Google Scholar]
  23. Sprouse J. S., Aghajanian G. K. Responses of hippocampal pyramidal cells to putative serotonin 5-HT1A and 5-HT1B agonists: a comparative study with dorsal raphe neurons. Neuropharmacology. 1988 Jul;27(7):707–715. doi: 10.1016/0028-3908(88)90079-2. [DOI] [PubMed] [Google Scholar]
  24. Titeler M., Lyon R. A., Glennon R. A. Radioligand binding evidence implicates the brain 5-HT2 receptor as a site of action for LSD and phenylisopropylamine hallucinogens. Psychopharmacology (Berl) 1988;94(2):213–216. doi: 10.1007/BF00176847. [DOI] [PubMed] [Google Scholar]
  25. Tricklebank M. D., Forler C., Fozard J. R. The involvement of subtypes of the 5-HT1 receptor and of catecholaminergic systems in the behavioural response to 8-hydroxy-2-(di-n-propylamino)tetralin in the rat. Eur J Pharmacol. 1984 Nov 13;106(2):271–282. doi: 10.1016/0014-2999(84)90714-3. [DOI] [PubMed] [Google Scholar]
  26. Wozniak K. M., Aulakh C. S., Hill J. L., Murphy D. L. The effect of 8-OH-DPAT on temperature in the rat and its modification by chronic antidepressant treatments. Pharmacol Biochem Behav. 1988 Jun;30(2):451–456. doi: 10.1016/0091-3057(88)90479-0. [DOI] [PubMed] [Google Scholar]
  27. Yamawaki S., Lai H., Horita A. Dopaminergic and serotonergic mechanisms of thermoregulation: mediation of thermal effects of apomorphine and dopamine. J Pharmacol Exp Ther. 1983 Nov;227(2):383–388. [PubMed] [Google Scholar]
  28. Yap C. Y., Taylor D. A. Involvement of 5-HT2 receptors in the wet-dog shake behaviour induced by 5-hydroxytryptophan in the rat. Neuropharmacology. 1983 Jul;22(7):801–804. doi: 10.1016/0028-3908(83)90123-5. [DOI] [PubMed] [Google Scholar]

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