, Volume 119, Issue 1, pp 9–14 | Cite as

Acute immobilization stress reduces (±DOI)-induced 5-HT2A receptor-mediated head shakes in rats

  • S. Yamada
  • A. Watanabe
  • M. Nankai
  • M. Toru
Original Investigation


Acute immobilization stress induced by taping four limbs, applying tail pinch stress and electric foot shock stress immediately reduced the frequency of head shakes induced by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane ((±)DOI), a 5-HT2A/C agonist in rats. Immobilization stress due to the use of cylinder restraint and forced swimming did not affect 5-HT2A-mediated behavior. Acute immobilization stress did not affect [3H]ketanserin binding to the 5HT2A receptor in the prefrontal cortex and hippocampus. Presynaptic serotonergic lesions with 5,7-dihydroxytryptamine (5,7-DHT) did not affect the reduction in 5-HT2A-mediated behavior after acute immobilization stress. The decreases in head shake frequency after acute immobilization stress by taping were attenuated by pretreatment with diazepam (2.5 mg/kg IP): This attenuation was reversed by pretreatment with flumazenil (10 mg/kg IP). The reduction in (±)DOI- induced 5-HT2A-mediated behavior caused by stress may be related to a change in agonist affinity to the receptor or changes in other neurotransmitter systems or the effect of PI turnover.

Key words

DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) 5-HT2A Head shake Diazepam Immobilization stress [3H]Ketanserin binding 5,7-DHT (5,7-dihydroxytryptamine) 


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  1. Appel NM, Mitchell WM, Garlick RK, Glennon RA, Teitler M, DeSouza EB (1990) Autoradiographic characterization of (±)-1-(2,5-dimethoxy-4-[125I]iodophenyl)-2-aminopropane ([125I]DOI) binding to 5-HT2 and 5-HT1C receptors in rat brain. J Pharmacol Exp Ther 255:843–857Google Scholar
  2. Arnt J, Hyttel J (1989) Facilitation of 8-OH-DPAT-induced forepaw treading of rats by the 5-HT2 agonist DOI. Eur J Pharmacol 161:45–51Google Scholar
  3. Bedard P, Pycock CJ (1977) “Wet-dog” shake behavior in the rat: A possible quantitative model of central 5-hydroxytryptamine activity. Neuropharmacology 16:663–670Google Scholar
  4. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254Google Scholar
  5. Conn PJ, Sanders-Bush BE (1986) Regulation of serotonin-stimulated phosphoinositide hydrolysis: relation to the serotonin 5-HT-2 binding site. J Neurosci 6:3669–3675Google Scholar
  6. Curzon G, Joseph MH, Knott PJ (1972) Effect of immobilization and food deprivation on rat brain tryptophan metabolism. J Neurochem 19:1967–1974Google Scholar
  7. Darmani NA, Martin BR, Pandey U, Glennon RA (1990) Do functional relationships exist between 5-HT1A and 5-HT2 receptors? Pharmacol Biochem Behav 36:901–906Google Scholar
  8. Darmani NA, Martin BR, Glennon RA (1992) Repeated administration of low doses of cocaine enhances the sensitivity of 5-HT2 receptor function. Pharmacol Biochem Behav 41:519–527Google Scholar
  9. DeSouza RJ, Goodwin GM, Green AR, Heal DJ (1986) Effect of chronic treatment with 5-HT1 agonist (8-OH-DPAT and RU 24969) and antagonist (isapirone) drugs on the behavioural responses of mice to 5-HT1 and 5-HT2 agonists. Br J Pharmacol 89:377–384Google Scholar
  10. Eison AS, Yocca FD (1985) Reduction in cortical 5HT2 receptor sensitivity after continuous gepirone treatment. Eur J Pharmacol 111:389–392Google Scholar
  11. Eison AS, Yocca FD, Gianutsos G (1988) Noradrenergic denervation alters serotonin2-mediated behavior but not serotonin2 receptor number in rats: modulatory role of beta adrenergic receptors. J Pharmacol Exp Ther 246:571–577Google Scholar
  12. Glennon RA (1986) Discriminative stimulus properties of the serotonergic agent 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Life Sci 39:825–830Google Scholar
  13. Glennon RA (1990) Serotonin receptors: clinical implications. Neurosci Biobehav Rev 14:35–47Google Scholar
  14. Goodwin GM, Green AR, Johnson, P (1984) 5-HT2 receptor characteristics in frontal cortex and 5-HT2 receptor-mediated headtwitch behaviour following antidepressant treatment to mice. Br J Pharmacol 83:235–242Google Scholar
  15. Gray JA, Metz A, Goodwin GM, Green AR (1986) The effects of the GABA-mimetic drugs, progabide and baclofen, on the biochemistry and function of 5-hydroxytryptamine and noradrenaline. Neuropharmacology 25:711–716Google Scholar
  16. Javaid JI, Sahni SK, Pandey SC, Davis JM (1993) Repeated cocaine administration does not affect 5-HT receptor subtypes (5-HT1A, 5-HT2) in several rat brain regions. Eur J Pharmacol 238:425–429Google Scholar
  17. Kawanami T, Morinobu S, Totsuka S, Endoh M (1992) Influence of stress and antidepressant treatment on 5-HT-stimulated phosphoinositide hydrolysis in rat brain. Eur J Pharmacol 216:385–392Google Scholar
  18. Levine JD, Feldmesser M, Tecott L, Gordon N, Izdebski K (1984) Pain-induced vocalization in the rat and its modification by pharmacological agents. Brain Res 296:121–127Google Scholar
  19. Leysen JE, Niemegeers CJ, Van Nueten JM, Laduron PM (1982) [3H]-Ketanserin (R-41 468), a selective [3H]-ligand for serotonin2 receptor binding sites. Binding properties, brain distribution and functional role. Mol Pharmacol 21:301–314Google Scholar
  20. Leysen JE, Janssen PF, Niemegeers CJ (1989) Rapid desensitization and down regulation of 5-HT2 receptors by DOM treatment. Eur J Pharmacol 163:145–149Google Scholar
  21. Lombardi G, Gandolfi O, Dall'Olio R, Pellegrini GD, Beni M, Carla V, Consolazione A, Moroni F (1987) Lesioning and recovery of the serotoninergic profections to the hippocampus. Brain Res 411:275–281Google Scholar
  22. Lucki I, Minugh PN (1987) Serotonin-induced head shaking behavior in rats does not involve receptors located in the frontal cortex. Brain Res 420:403–406Google Scholar
  23. Mendelson SD, McEwen BS (1991) Autoradiographic analyses of the effects of restraint-induced stress on 5-HT1A, 5-HT1C and 5-HT2 receptors in the dorsal hippocampus of male and female rats. Neuroendocrinology 54:454–461Google Scholar
  24. Metz A, Heal DJ (1986) In mice repeated administration of electroconvulsive shock or desmethylimipramine produces rapid alterations in 5-HT2-mediated head-twitch responses and cortical 5-HT2 receptor number. Eur J Pharmacol 126:159–162Google Scholar
  25. Metz A, Goodsin GM, Green AR (1985) The administration of baclofen to mice increases 5-HT2-mediated head-twitch behaviour and 5-HT2 receptor number in frontal cortex. Neuropharmacology 24:357–360Google Scholar
  26. Morinobu S, Kuwayama N, Kawanami T, Okuyama N, Takahashi M, Totsuka S, Endoh M (1992) Influence of the acute stress on agonist-stimulated phosphoinositede hydrolysis in the rat cerebral cortex. Prog Neuropsychopharmacol Biol Psychiatry 16:561–570Google Scholar
  27. Oliveira MP, Campos MF (1993) Behavioral effects of the intraventricular administration of 5-HT and dopamine in the common marmoset (Callithrix jacchus). Pharmacol Biochem Behav 46:21–25Google Scholar
  28. Pandey SC, Piano MR, Schwertz DW, Davis JM, Pandey GN (1992) Effect of Ethanol administration and withdrawal on serotonin receptor subtypes and receptor-mediated phosphoinositide hydrolysis in rat brain. Alcohol Clin Exp Res 16:1110–1116Google Scholar
  29. Smith RL, Barrett RJ, Sanders-Bush E (1990) Adaptation of brain 5HT2 receptors after mianserin treatment: receptor sensitivity, not receptor binding, more accurately correlates with behavior. J Pharmacol Exp Ther 254:484–488Google Scholar
  30. Wieland S, Kreider MS, McGonigle P, Lucki I (1990) Destruction of the nucleus raphe obscurus and potentiation of serotoninmediated behaviors following administration of the neurotoxin 3-acetylpyridine. Brain Res 520:291–302Google Scholar
  31. Yocca FD, Wright RN, Margraf RR, Eison AS (1990) 8-OH-DPAT and buspirone analogs inhibit the ketanserin-sensitive quipazine-induced head shake response in rats. Pharmacol Biochem Behav 35:251–254Google Scholar
  32. Zamifir O, Broqua P, Baudrie V, Chaouloff F (1992) Effects of cold stress on some 5HT1A, 5HT1C and 5HT2 receptor-mediated responses. Eur J Pharmacol 219:261–269Google Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • S. Yamada
    • 1
  • A. Watanabe
    • 1
  • M. Nankai
    • 1
  • M. Toru
    • 1
  1. 1.Department of Neuropsychiatry, Faculty of MedicineTokyo Medical and Dental UniversityBunkyo-ku, TokyoJapan

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