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Gene Review

Htr1a  -  5-hydroxytryptamine (serotonin) receptor 1A

Mus musculus

Synonyms: 5-HT-1A, 5-HT1A, 5-HT1A receptor, 5-hydroxytryptamine receptor 1A, Gpcr18, ...
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Disease relevance of Htr1a

  • In mice TVX Q 7821 produced a dose-dependent inhibition of the hypothermia induced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) with an ED50 of 5.3 mg/kg suggesting that TVX Q 7821 was an antagonist of the presynaptic (possibly somato-dendritic) 5-HT1A receptor [1].
  • The presence of receptor RNA in differentiated SN-48 cells correlated with the appearance of functional responses (i.e., pertussis toxin-sensitive inhibition of cAMP accumulation) to 5-HT1A agonists in differentiated but not in undifferentiated cells [2].
  • Since fluoxetine has been shown to be useful in the treatment of eating disorders and to promote weight loss in obese humans, although at doses greater than those required for the treatment of depression, a combination of fluoxetine with a 5HT1A receptor antagonist could be of clinical utility in the treatment of eating disorders and obesity [3].
  • Besides their proved anxiolytic action, agonists of the 5-HT1A receptor subtype show prospects as antidepressants or neuroprotective agents in case of ischemia [4].
  • Medial hypothalamic 5-hydroxytryptamine (5-HT)1A receptors regulate neuroendocrine responses to stress and exploratory locomotor activity: application of recombinant adenovirus containing 5-HT1A sequences [5].

Psychiatry related information on Htr1a


High impact information on Htr1a

  • Recently a new drug, 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT), has been identified which shows high selectivity for binding to 5-HT1 (possibly 5-HT1A) receptors and which binds to presynaptic serotonin autoreceptors in some regions of rat brain [11].
  • However, the hyperlocomotor effect of the 5-HT1A/1B agonist RU24969 was absent in mutant mice, indicating that this effect is mediated by 5-HT1B receptors [12].
  • The outward currents evoked by agonists for GABA(B) receptors, 5HT1A receptors, and adenosine A1 receptors were essentially absent in mutant mice, while the inward current evoked by muscarinic receptor activation was unaltered [13].
  • Local increase of 5-hydroxytryptamine 1a receptor expression in medial amygdala may contribute to these changes [14].
  • Heterozygote 5-HT1A mutants expressed approximately one-half of wild-type receptor density and displayed intermediate phenotypes in most behavioral tests [15].

Chemical compound and disease context of Htr1a


Biological context of Htr1a


Anatomical context of Htr1a

  • Among 5-HT1 receptors, the 5-HT1A receptor transcript is expressed densely in E14.5-16.5 thalamus, in hippocampus, and in a medial to lateral gradient in cortex, whereas the 5-HT1B receptor mRNA is expressed in more lateral parts of the dorsal thalamus and in the striatum at these ages [23].
  • Using receptor subtype-specific riboprobes and in situ hybridization, we observed that all 5-HT1 receptor subtypes are expressed as early as embryonic day (E) 14.5 in the forebrain, typically in gradients within specific structures [23].
  • Moreover, all members of the 5-HT1 receptor class are strongly and transiently expressed in the embryonic dorsal thalamus, which suggests a potential role for serotonin in early thalamic development [23].
  • Opposite responses in the same pyramidal neuron could be evoked by stimulating the raphe nuclei at different coordinates, suggesting a precise connectivity between 5-HT neuronal subgroups and 5-HT1A and 5-HT2A receptors in pyramidal neurons [24].
  • In hippocampal neuronal cultures, 5-HT1A receptors are expressed on somatodendritic membranes but are absent from axons [25].

Associations of Htr1a with chemical compounds

  • Regional changes in density of serotonin transporter in the brain of 5-HT1A and 5-HT1B knockout mice, and of serotonin innervation in the 5-HT1B knockout [19].
  • 4. RU 24969 (7.5 mg kg-1 i.p.)-induced hyperlocomotion was inhibited by the (-)-, but not (+)-isomers of pindolol (4 mg kg-1) and propranolol (20 mg kg-1) but not by metoprolol (10 mg kg-1) or ICI 118,551 (5 mg kg-1), consistent with an involvement of 5-HT1A or 5-HT1B receptors [26].
  • Spiperone, propranolol and pindolol (mixed 5-HT1A and 5-HT1B antagonists) effectively reversed both the tail-flick facilitation and the antagonistic effect on morphine sulfate-induced antinociception produced by 8-OH-DPAT and 5-CT [27].
  • This effect of 8-OH-DPAT was minimally attenuated by the selective 5-HT1A receptor antagonist WAY 100635 but was reversibly and significantly reduced in the presence of ritanserin, a mixed 5-HT(2/7) receptor antagonist [28].
  • The effect of the selective 5-hydroxytryptamine1B (5-HT1B) receptor agonist 5-propoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-pyrrolo[3,2-b]pyridine (CP 94253) and the 5-HT1A/1B/1D receptor agonist 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridyl)-1H-indole (RU 24969) in maximal electroshock- and pentylenetetrazol-induced seizures in mice was examined [29].

Physical interactions of Htr1a


Regulatory relationships of Htr1a


Other interactions of Htr1a

  • In the present group of experiments, we evaluate the role of 5-HT1A, 5-HT1B and 5-HT2A receptors in mCPP-induced hyperactivity in 5-HT2C KO mice [35].
  • The effectiveness with which M100907 antagonizes the behavioral actions of this compound, coupled with the lack of significant antagonist effects of WAY-100635, strongly suggests that the 5-HT 2A receptor is an important site of action for 5-MeO-DIPT, despite its apparent in vitro selectivity for the 5-HT 1A receptor [36].
  • Moreover, activation of 5-HT7 receptors in the mouse SCN, but not 5-HT1A receptors, also results in a reduction in the amplitude of the optic nerve-evoked EPSC [28].
  • Blockade of HHTC activation induced by the presence of females appears to involve 5-HT1A and 5-HT2C receptors, while activation involves 5-HT2A and 5-HT3 receptors [37].
  • Glucocorticoid receptor-dependent desensitization of 5-HT1A autoreceptors by sleep deprivation: studies in GR-i transgenic mice [8].

Analytical, diagnostic and therapeutic context of Htr1a


  1. 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. Goodwin, G.M., De Souza, R.J., Green, A.R. Psychopharmacology (Berl.) (1986) [Pubmed]
  2. Cloning and differentiation-induced expression of a murine serotonin1A receptor in a septal cell line. Charest, A., Wainer, B.H., Albert, P.R. J. Neurosci. (1993) [Pubmed]
  3. 5HT1A receptor antagonists enhance the functional activity of fluoxetine in a mouse model of feeding. Li, D.L., Simmons, R.M., Iyengar, S. Brain Res. (1998) [Pubmed]
  4. Biochemical, electrophysiological and neurohormonal studies with B-20991, a selective 5-HT1A receptor agonist. Caicoya, A.G., Beneytez, M.E., Delgado, M., Manzanares, J., López-Rodríguez, M.L., Benhamu, B., Morcillo, M.J., Pozo, M.A., Rubia, F.J., Fuentes, J.A. Pharmacology (2001) [Pubmed]
  5. Medial hypothalamic 5-hydroxytryptamine (5-HT)1A receptors regulate neuroendocrine responses to stress and exploratory locomotor activity: application of recombinant adenovirus containing 5-HT1A sequences. Li, Q., Holmes, A., Ma, L., Van de Kar, L.D., Garcia, F., Murphy, D.L. J. Neurosci. (2004) [Pubmed]
  6. Key role of 5-HT1B receptors in the regulation of paradoxical sleep as evidenced in 5-HT1B knock-out mice. Boutrel, B., Franc, B., Hen, R., Hamon, M., Adrien, J. J. Neurosci. (1999) [Pubmed]
  7. 3,4-N-methlenedioxymethamphetamine-induced hypophagia is maintained in 5-HT1B receptor knockout mice, but suppressed by the 5-HT2C receptor antagonist RS102221. Conductier, G., Crosson, C., Hen, R., Bockaert, J., Compan, V. Neuropsychopharmacology (2005) [Pubmed]
  8. Glucocorticoid receptor-dependent desensitization of 5-HT1A autoreceptors by sleep deprivation: studies in GR-i transgenic mice. Evrard, A., Barden, N., Hamon, M., Adrien, J. Sleep. (2006) [Pubmed]
  9. The effects of acute and repeated administration of T3 to mice on 5-HT1 and 5-HT2 function in the brain and its influence on the actions of repeated electroconvulsive shock. Heal, D.J., Smith, S.L. Neuropharmacology (1988) [Pubmed]
  10. The pharmacology of the 5-HT4 receptor. Costall, B., Naylor, R.J. International clinical psychopharmacology. (1993) [Pubmed]
  11. Presynaptic serotonin receptor-mediated response in mice attenuated by antidepressant drugs and electroconvulsive shock. Goodwin, G.M., De Souza, R.J., Green, A.R. Nature (1985) [Pubmed]
  12. Enhanced aggressive behavior in mice lacking 5-HT1B receptor. Saudou, F., Amara, D.A., Dierich, A., LeMeur, M., Ramboz, S., Segu, L., Buhot, M.C., Hen, R. Science (1994) [Pubmed]
  13. G protein-coupled inwardly rectifying K+ channels (GIRKs) mediate postsynaptic but not presynaptic transmitter actions in hippocampal neurons. Lüscher, C., Jan, L.Y., Stoffel, M., Malenka, R.C., Nicoll, R.A. Neuron (1997) [Pubmed]
  14. Increased anxiety and synaptic plasticity in estrogen receptor beta -deficient mice. Krezel, W., Dupont, S., Krust, A., Chambon, P., Chapman, P.F. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  15. Serotonin receptor 1A knockout: an animal model of anxiety-related disorder. Ramboz, S., Oosting, R., Amara, D.A., Kung, H.F., Blier, P., Mendelsohn, M., Mann, J.J., Brunner, D., Hen, R. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  16. Analysis of the nature of antagonism of the reserpine-induced hypothermia by imipramine. Francès, H. Naunyn Schmiedebergs Arch. Pharmacol. (1987) [Pubmed]
  17. Behavioural and pharmacological characterisation of the canopy stretched attend posture test as a model of anxiety in mice and rats. Grewal, S.S., Shepherd, J.K., Bill, D.J., Fletcher, A., Dourish, C.T. Psychopharmacology (Berl.) (1997) [Pubmed]
  18. S 14671: a naphtylpiperazine 5-hydroxytryptamine1A agonist of exceptional potency and high efficacy possessing antagonist activity at 5-hydroxytryptamine1C/2 receptors. Millan, M.J., Rivet, J.M., Canton, H., Lejeune, F., Bervoets, K., Brocco, M., Gobert, A., Lefebvre de Ladonchamps, B., Le Marouille-Girardon, S., Verriele, L. J. Pharmacol. Exp. Ther. (1992) [Pubmed]
  19. Regional changes in density of serotonin transporter in the brain of 5-HT1A and 5-HT1B knockout mice, and of serotonin innervation in the 5-HT1B knockout. Ase, A.R., Reader, T.A., Hen, R., Riad, M., Descarries, L. J. Neurochem. (2001) [Pubmed]
  20. 5-HT1B receptor knockout, but not 5-HT1A receptor knockout mice, show reduced startle reactivity and footshock-induced sensitization, as measured with the acoustic startle response. Dirks, A., Pattij, T., Bouwknecht, J.A., Westphal, T.T., Hijzen, T.H., Groenink, L., van der Gugten, J., Oosting, R.S., Hen, R., Geyer, M.A., Olivier, B. Behav. Brain Res. (2001) [Pubmed]
  21. 3-amino-3,4-dihydro-2H-1-benzopyran derivatives as 5-HT1A receptor ligands and potential anxiolytic agents. 2. Synthesis and quantitative structure-activity relationship studies of spiro[pyrrolidine- and piperidine-2,3'(2'H)-benzopyrans]. Comoy, C., Marot, C., Podona, T., Baudin, M.L., Morin-Allory, L., Guillaumet, G., Pfeiffer, B., Caignard, D.H., Renard, P., Rettori, M.C., Adam, G., Guardiola-Lemaitre, B. J. Med. Chem. (1996) [Pubmed]
  22. Serotonin receptor activation leads to neurite outgrowth and neuronal survival. Fricker, A.D., Rios, C., Devi, L.A., Gomes, I. Brain Res. Mol. Brain Res. (2005) [Pubmed]
  23. Expression mapping of 5-HT1 serotonin receptor subtypes during fetal and early postnatal mouse forebrain development. Bonnin, A., Peng, W., Hewlett, W., Levitt, P. Neuroscience (2006) [Pubmed]
  24. Co-expression and in vivo interaction of serotonin1A and serotonin2A receptors in pyramidal neurons of prefrontal cortex. Amargós-Bosch, M., Bortolozzi, A., Puig, M.V., Serrats, J., Adell, A., Celada, P., Toth, M., Mengod, G., Artigas, F. Cereb. Cortex (2004) [Pubmed]
  25. Differential addressing of 5-HT1A and 5-HT1B receptors in epithelial cells and neurons. Ghavami, A., Stark, K.L., Jareb, M., Ramboz, S., Ségu, L., Hen, R. J. Cell. Sci. (1999) [Pubmed]
  26. Evidence that RU 24969-induced locomotor activity in C57/B1/6 mice is specifically mediated by the 5-HT1B receptor. Cheetham, S.C., Heal, D.J. Br. J. Pharmacol. (1993) [Pubmed]
  27. Differential roles of 5-hydroxytryptamine1A and 5-hydroxytryptamine1B receptor subtypes in modulating spinal nociceptive transmission in mice. Alhaider, A.A., Wilcox, G.L. J. Pharmacol. Exp. Ther. (1993) [Pubmed]
  28. Serotonergic modulation of retinal input to the mouse suprachiasmatic nucleus mediated by 5-HT1B and 5-HT7 receptors. Smith, B.N., Sollars, P.J., Dudek, F.E., Pickard, G.E. J. Biol. Rhythms (2001) [Pubmed]
  29. Anticonvulsant effect of the selective 5-HT1B receptor agonist CP 94253 in mice. Wesołowska, A., Nikiforuk, A., Chojnacka-Wójcik, E. Eur. J. Pharmacol. (2006) [Pubmed]
  30. Regulation of hippocampal 5-HT1A receptor mRNA and binding in transgenic mice with a targeted disruption of the glucocorticoid receptor. Meijer, O.C., Cole, T.J., Schmid, W., Schütz, G., Joëls, M., De Kloet, E.R. Brain Res. Mol. Brain Res. (1997) [Pubmed]
  31. Inhibitors of serotonin synthesis and antagonists of serotonin 1A receptors inhibit T lymphocyte function in vitro and cell-mediated immunity in vivo. Aune, T.M., Golden, H.W., McGrath, K.M. J. Immunol. (1994) [Pubmed]
  32. Role of the inhibitory adrenergic alpha 2 and serotonergic 5-HT1A components of cocaine's actions on the DOI-induced head-twitch response in 5-HT2-receptor supersensitive mice. Darmani, N.A. Pharmacol. Biochem. Behav. (1993) [Pubmed]
  33. Ethanol consumption and serotonin-1A (5-HT1A) receptor function in heterozygous BDNF (+/-) mice. Hensler, J.G., Ladenheim, E.E., Lyons, W.E. J. Neurochem. (2003) [Pubmed]
  34. High intensity social conflict in the Swiss albino mouse induces analgesia modulated by 5-HT1A receptors. Canto de Souza, A., Nunes de Souza, R.L., Péla, I.R., Graeff, F.G. Pharmacol. Biochem. Behav. (1997) [Pubmed]
  35. mCPP-induced hyperactivity in 5-HT2C receptor mutant mice is mediated by activation of multiple 5-HT receptor subtypes. Dalton, G.L., Lee, M.D., Kennett, G.A., Dourish, C.T., Clifton, P.G. Neuropharmacology (2004) [Pubmed]
  36. Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats. Fantegrossi, W.E., Harrington, A.W., Kiessel, C.L., Eckler, J.R., Rabin, R.A., Winter, J.C., Coop, A., Rice, K.C., Woods, J.H. Pharmacol. Biochem. Behav. (2006) [Pubmed]
  37. The roles of different types of serotonin receptors in activation of the hypophyseal-testicular complex induced in mice by the presence of a female. Amstislavskaya, T.G., Popova, N.K. Neurosci. Behav. Physiol. (2004) [Pubmed]
  38. Elevated anxiety and antidepressant-like responses in serotonin 5-HT1A receptor mutant mice. Heisler, L.K., Chu, H.M., Brennan, T.J., Danao, J.A., Bajwa, P., Parsons, L.H., Tecott, L.H. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
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