Activation of 5-HT1A receptors by their agonist 5-OH-DPAT (0.1, 0.5. and 1.0 mg/kg, i.p.) produced a significant and dose-dependent decrease in the number of headshakes mediated by 5-HT2A receptors, while blockade of 5-HT1A receptors by their antagonist WAT-100635 (0.5 and 1.0 mg/kg, i.p.), conversely, induced a significant increase in this functional response to 5-HT2A receptors. At the same time, activation of 5-HT2A receptors by their agonist DOI (0.5 and 1.0 mg/kg, i.p.) prevented the hypothermic response mediated by 5-HT1A receptors, while blockade of 5-HT2A receptors with ketanserin (1.0 and 2.0 mg/kg, i.p.) enhanced this functional response of 5-HT1A receptors. In addition, ketanserin (1.0 and 2.0 mg/kg, i.p. or 20 and 40 nmol, i.c.v.) induced a dose-dependent hypothermic response. This ketanserin (40 nmol, i.c.v.)-induced hypothermic response was significantly weakened by prior administration of the 5-HT1A receptor antagonist WAY-100635 (1.0 mg/kg, i.p.). This suggests that the hypothermic response evoked by blockade of 5-HT2A receptors is partially mediated by 5-HT1A receptors. These data point to the existence of a bidirectional functional interaction between 5-HT1A and 5-HT2A receptors, such that these receptors can support the mutual regulation of functional activity.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Abdel-Fattah, A. F., Matsumoto, K, el-Hady, K. A., and Watanabe, H., “5-HT1A and 5-HT2 receptors mediate hypo- and hyperthermic effects of tryptophan in pargyline-pretreated rats,” Pharmacol. Biochem. Behav., 52, No. 2, 379–384 (1995).
Albert, P. R. and Lemonde, S., “5-HT1A receptors, gene repression, and depression: guilt by association,” Neuroscientist, 10, No. 6, 575–593 (2004).
Blier, P., Seletti, B., Gilbert, F., et al., “Serotonin 1A receptor activation and hypothermia in humans: lack of evidence for a presynaptic mediation,” Neuropsychopharmacol., 27, No. 2, 301–308 (2002).
Chaiseha, Y., Kang, S. W., Leclerc, B., et al., “Serotonin receptor subtypes influence prolactin secretion in the turkey,” Gen. Comp. Endocrinol., 165, No. 1, 170–175 (2010).
Delaney, C., Gien, J., Grover, T. R., et al., “Pulmonary vascular effects of sero tonin and selective serotonin reuptake inhibitors in the late-gestation ovine fetus,” Am. J. Physiol. Lung Cell. Mol. Physiol., 301, No. 6, L937–944 (2011).
Egashira, N., Koushi, E., Mishima, K., et al., “2,5-Dimethoxy-4-iodoamphe tamine (DOI) inhibits Delta9-tetrahydrocannabinol-induced catalepsy-like immobilization in mice,” J. Pharmacol. Sci., 1–5, No. 4, 361–366 (2007).
Fox, M. A., Stein, A. R., French, H. T., and Murphy, D. L., “Functional interactions between 5-HT2A and presynaptic 5-HT1A receptor-based responses in mice genetically deficient in the serotonin 5-HT transporter (SERT),” Br. J. Pharmacol., 159, No. 4, 879–887 (2010).
Franklin, J. M. and Carrasco, G. A., “G-protein receptor kinase 5 regulates the cannabinoid receptor 2-induced up-regulation of serotonin 2A receptors,” J. Biol. Chem., 288, No. 22, 15,712–15,724 (2013).
Gaggi, R., Dall’Olio, R., and Roncada, P., “Effect of the selective 5-HT receptor agonists 8-OHDPAT and DOI on behavior and brain biogenic amines of rats,” Gen. Pharmacol., 28, No. 4, 583–587 (1997).
Green, A. R. and Heal, D. J., “The effects of drugs on serotonin-mediated behavioural models,” in: Neuropharmacology of Serotonin, Oxford University Press, Oxford (1985), pp. 326–365.
Hensler, J. G. and Truett, K. A., “Effect of chronic serotonin-2 receptor agonist or antagonist administration on serotonin-1A receptor sensitivity,” Neuropsychopharmacol., 19, No. 5, 354–364 (1998).
Herremans, A. H., van der Heyden, J. A., van Drimmelen M., and Olivier, B., “The 5-HT1A receptor agonist flesinoxan shares discriminative stimulus properties with some 5-HT2 receptor antagonists,” Pharmacol. Biochem. Behav., 64, No. 2, 389–395 (1999).
Kalkman, H. O., Neumann, V., Nozulak, J., and Tricklebank, M. D., “Cataleptogenic effect of subtype selective 5-HT receptor antagonists in the rat,” Eur. J. Pharmacol., 343, No. 2–3, 201–207 (1998).
Kondaurova, E. M., Naumenko, V. S., and Popova, N. K., “Effect of chronic activation of 5-HT3 receptors on 5-HT3, 5-HT1A and 5-HT2A receptors functional activity and expression of key genes of the brain serotonin system,” Neurosci. Lett., 522, No. 1, 52–56 (2012).
Mazzola-Pomietto, P., Aulakh, C. S., Wozniak, K. M., et al., “Evidence that 1-(2,5-dimethoxy-4-iodopheny1)-2-aminopropane (DOI)-induced hyperthermia in rats is mediated by stimulation of 5-HT2A receptors,” Psychopharmacology (Berlin), 117, No. 2, 193–199 (1995).
Naumenko, K. S., Bazovkina, D. V., Kondaurova, E. M., et al., “The role of 5-HT2A receptor and 5-HT2A/5HT1A receptor interaction in the suppression of catalepsy,” Genes Brain Behav., 9, No. 5, 519–524 (2010).
Naumenko, V. S., Kondaurova, E. M., and Popova, N. K., “Central 5-HT3 receptor-induced hypothermia in mice: interstrain differences and comparison with hypothermia mediated via 5-HT1A receptor,” Neurosci. Lett., 465, No. 1, 50–54 (2009).
Naumenko, V. S., Kondaurova, E. M., and Popova N. K., “On the role of brain 5-HT7 receptor in the mechanism of hypothermia: comparison with hypothermia mediated via 5-HT1A and 5-HT3 receptor,” Neuropharmacol., 61, No. 8, 1360–1365 (2011).
Overstreet, D. H., Rezvani, A. H., Knapp, D. J., et al., “Further selection of rat lines differing in 5-HT1A receptor sensitivity: behavioral and functional correlates,” Psychiatr. Genet., 6, No. 3, 107–117 (1996).
Popova N. K. and Naumenko, V. S., “5-HT1A receptor as a key player in the brain 5-HT system,” Rev. Neurosci., 24, No. 2, 191–204 (2013).
Raymond, J. R., “Protein kinase C induces phosphorylation and desensitization of the human 5-HT1A receptor,” J. Biol. Chem., 266, No. 22, 14747–14753 (1991).
Slotnick, B. M. and Leonard, C. M., A Stereotaxic Atlas of the Albino Mouse Forebrain, US Dept. of Health, Education and Welfare, Rockville, Maryland (1975).
Takao, K, Nagatani, T., Kitamura, Y., and Yamawaki, S., “Effects of corticosterone on 5-HT1A and 5-HT2 receptor binding and on the receptor-mediated behavioral responses of rats,” Eur. J. Pharmacol., 333, No. 2–3, 123–128 (1997).
Valdez, M., Burke, T. F., and Hensler, J. G., “Selective heterologous regulation of 5-HT1A receptor-stimulated 35S GTPgammaS binding in the anterior cingulate cortex as a result of 5-HT2 receptor activation,” Brain Res., 957, No. 1, 174–182 (2002).
Won, S. J. and Lin, M. T., “5-Hydroxytryptamine receptors in the hypothalamus mediate thermoregulatory responses in rabbits,” Naunyn. Schmiedebergs Arch. Pharmacol., 338, No. 3, 256–261 (1988).
Zhang, Y., D’Souza, D., Raap, D. K., et al., “Characterization of the functional heterologous desensitization of hypothalamic 5-HT(1A) receptors after 5-HT(2A) receptor activation,” J. Neurosci., 21, No. 20, 7919–7927 (2001).
Zhang, Y., Gray, T. S., D’Souza, D. N., et al., “Desensitization of 5-HT1A receptors by 5-HT2A receptors in neuroendocrine neurons in vivo,” J. Pharmacol. Exp. Ther., 310, No. 1, 59–66 (2004).
Zifa, E. and Fillion, G., “5-Hydroxytryptamine receptors,” Pharmacol. Rev., 44, No. 3, 401–458 (1992).
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 65, No. 2, pp. 240–247, March–April, 2015. Original article submitted July 21, 2014. Accepted December 22, 2014.
Rights and permissions
About this article
Cite this article
Naumenko, V.S., Bazovkina, D.V. & Kondaurova, E.M. Functional Interactions between 5-HT1A and 5-HT2A Receptors in the Brain. Neurosci Behav Physi 46, 783–788 (2016). https://doi.org/10.1007/s11055-016-0311-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11055-016-0311-0