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. 1992 Sep;107(1):15–21. doi: 10.1111/j.1476-5381.1992.tb14457.x

Characterization of 8-OH-DPAT-induced hypothermia in mice as a 5-HT1A autoreceptor response and its evaluation as a model to selectively identify antidepressants.

K F Martin 1, I Phillips 1, M Hearson 1, M R Prow 1, D J Heal 1
PMCID: PMC1907611  PMID: 1422568

Abstract

1. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) dose-dependently induced hypothermia in mice. 2. The 5-HT1A receptor partial agonists, buspirone, gepirone and ipsapirone, also dose-dependently induced hypothermia. 3. The 8-OH-DPAT temperature response was antagonized by the 5-HT1 receptor antagonists quipazine (2 mg kg-1, i.p.), (+/-)-propranolol (10 mg kg-1, i.p.). (+/-)-pindolol (5 mg kg-1, i.p.), spiroxatrine (0.5 mg kg-1, i.p.) and metitepine (0.05 mg kg-1, i.p.), but not by 5-HT2 (ketanserin) or 5-HT3 (MDL 72222, GR 38032F) receptor antagonists. 4. The response was also antagonized by the dopamine D2 receptor antagonists, haloperidol and BRL 34778. No other catecholamine or muscarinic receptors were involved in mediating the response. 5. Destruction of 5-hydroxytryptamine (5-HT)-containing neurones with the neurotoxin, 5,7-dihydroxytryptamine (75 micrograms, i.c.v.), abolished the response to 8-OH-DPAT indicating that the 5-HT1A receptors involved were located on 5-HT neurones. 6. Chronic antidepressant treatment down-regulated this 8-OH-DPAT response. In addition, chronic administration of anxiolytics and neuroleptics was also effective in this respect. Down-regulation was also observed following repeated administration of 8-OH-DPAT (0.5 mg kg-1, s.c.), (+/-)-pindolol (10 mg kg-1, i.p.) and ketanserin (0.5 mg kg-1, i.p.). 7. In conclusion, these data confirm that 8-OH-DPAT-induced hypothermia is mediated by 5-HT1A autoreceptors. They also indicate that the response involves D2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Blier P., de Montigny C., Chaput Y. Modifications of the serotonin system by antidepressant treatments: implications for the therapeutic response in major depression. J Clin Psychopharmacol. 1987 Dec;7(6 Suppl):24S–35S. [PubMed] [Google Scholar]
  2. Blier P., de Montigny C. Modification of 5-HT neuron properties by sustained administration of the 5-HT1A agonist gepirone: electrophysiological studies in the rat brain. Synapse. 1987;1(5):470–480. doi: 10.1002/syn.890010511. [DOI] [PubMed] [Google Scholar]
  3. Blier P., de Montigny C., Tardif D. Effects of the two antidepressant drugs mianserin and indalpine on the serotonergic system: single-cell studies in the rat. Psychopharmacology (Berl) 1984;84(2):242–249. doi: 10.1007/BF00427453. [DOI] [PubMed] [Google Scholar]
  4. Goldberg H. L., Finnerty R. J. The comparative efficacy of buspirone and diazepam in the treatment of anxiety. Am J Psychiatry. 1979 Sep;136(9):1184–1187. doi: 10.1176/ajp.136.9.1184. [DOI] [PubMed] [Google Scholar]
  5. Goodwin G. M., De Souza R. J., Green A. R. Presynaptic serotonin receptor-mediated response in mice attenuated by antidepressant drugs and electroconvulsive shock. Nature. 1985 Oct 10;317(6037):531–533. doi: 10.1038/317531a0. [DOI] [PubMed] [Google Scholar]
  6. Goodwin G. M., De Souza R. J., Green A. R. The effects of a 5-HT1 receptor ligand isapirone (TVX Q 7821) on 5-HT synthesis and the behavioural effects of 5-HT agonists in mice and rats. Psychopharmacology (Berl) 1986;89(3):382–387. doi: 10.1007/BF00174379. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. Green A. R., Goodwin G. M., De Souza R. J., Heal D. J. The beta 2-adrenoceptor agonists clenbuterol and salbutamol enhance the hypothermic action of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in mice by a central mechanism. Neuropharmacology. 1986 Jan;25(1):21–24. doi: 10.1016/0028-3908(86)90053-5. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Heal D. J. Phenylephrine-induced activity in mice as a model of central alpha 1-adrenoceptor function. Effects of acute and repeated administration of antidepressant drugs and electroconvulsive shock. Neuropharmacology. 1984 Nov;23(11):1241–1251. doi: 10.1016/0028-3908(84)90040-6. [DOI] [PubMed] [Google Scholar]
  12. Hibert M., Middlemiss D. N. Stereoselective blockade at the 5-HT autoreceptor and inhibition of radioligand binding to central 5-HT recognition sites by the optical isomers of methiothepin. Neuropharmacology. 1986 Jan;25(1):1–4. doi: 10.1016/0028-3908(86)90050-x. [DOI] [PubMed] [Google Scholar]
  13. Higgins G. A., Bradbury A. J., Jones B. J., Oakley N. R. Behavioural and biochemical consequences following activation of 5HT1-like and GABA receptors in the dorsal raphé nucleus of the rat. Neuropharmacology. 1988 Oct;27(10):993–1001. doi: 10.1016/0028-3908(88)90058-5. [DOI] [PubMed] [Google Scholar]
  14. Hjorth S., Carlsson A. Is pindolol a mixed agonist-antagonist at central serotonin (5-HT) receptors? Eur J Pharmacol. 1986 Sep 23;129(1-2):131–138. doi: 10.1016/0014-2999(86)90344-4. [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. Hutson P. H., Donohoe T. P., Curzon G. Hypothermia induced by the putative 5-HT1A agonists LY165163 and 8-OH-DPAT is not prevented by 5-HT depletion. Eur J Pharmacol. 1987 Nov 10;143(2):221–228. doi: 10.1016/0014-2999(87)90536-x. [DOI] [PubMed] [Google Scholar]
  17. Leysen J. E., Van Gompel P., Gommeren W., Woestenborghs R., Janssen P. A. Down regulation of serotonin-S2 receptor sites in rat brain by chronic treatment with the serotonin-S2 antagonists: ritanserin and setoperone. Psychopharmacology (Berl) 1986;88(4):434–444. doi: 10.1007/BF00178504. [DOI] [PubMed] [Google Scholar]
  18. Marsden C. A., Martin K. F. Involvement of 5-HT1A- and alpha 2-receptors in the decreased 5-hydroxytryptamine release and metabolism in rat suprachiasmatic nucleus after intravenous 8-hydroxy-2-(n-dipropylamino) tetralin. Br J Pharmacol. 1986 Oct;89(2):277–286. doi: 10.1111/j.1476-5381.1986.tb10257.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Martin K. F., Mason R. Isapirone is a partial agonist at 5-hydroxytryptamine 1A (5-HT1A) receptors in the rat hippocampus: electrophysiological evidence. Eur J Pharmacol. 1987 Sep 23;141(3):479–483. doi: 10.1016/0014-2999(87)90569-3. [DOI] [PubMed] [Google Scholar]
  20. Middlemiss D. N., Fozard J. R. 8-Hydroxy-2-(di-n-propylamino)-tetralin discriminates between subtypes of the 5-HT1 recognition site. Eur J Pharmacol. 1983 May 20;90(1):151–153. doi: 10.1016/0014-2999(83)90230-3. [DOI] [PubMed] [Google Scholar]
  21. Middlemiss D. N. Stereoselective blockade at [3H]5-HT binding sites and at the 5-HT autoreceptor by propranolol. Eur J Pharmacol. 1984 Jun 1;101(3-4):289–293. doi: 10.1016/0014-2999(84)90173-0. [DOI] [PubMed] [Google Scholar]
  22. Nelson D. L., Taylor E. W. Spiroxatrine: a selective serotonin1A receptor antagonist. Eur J Pharmacol. 1986 May 13;124(1-2):207–208. doi: 10.1016/0014-2999(86)90147-0. [DOI] [PubMed] [Google Scholar]
  23. Pedigo N. W., Yamamura H. I., Nelson D. L. Discrimination of multiple [3H]5-hydroxytryptamine binding sites by the neuroleptic spiperone in rat brain. J Neurochem. 1981 Jan;36(1):220–226. doi: 10.1111/j.1471-4159.1981.tb02397.x. [DOI] [PubMed] [Google Scholar]
  24. Verge D., Daval G., Patey A., Gozlan H., el Mestikawy S., Hamon M. Presynaptic 5-HT autoreceptors on serotonergic cell bodies and/or dendrites but not terminals are of the 5-HT1A subtype. Eur J Pharmacol. 1985 Jul 31;113(3):463–464. doi: 10.1016/0014-2999(85)90099-8. [DOI] [PubMed] [Google Scholar]
  25. 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]

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