Abstract
We report that l-5-hydroxytryptophan (5-HTP), a serotonin precursor, resets the overt circadian rhythm in the Indian pygmy field mouse, Mus terricolor, in a phase- and dose-dependent manner. We used wheel running to assess phase shifts in the free-running locomotor activity rhythm. Following entrainment to a 12:12 h light–dark cycle, 5-HTP (100 mg/kg in saline) was intraperitoneally administered in complete darkness at circadian time (CT)s 0, 3, 6, 9, 12, 15, 18, and 21, and the ensuing phase shifts in the locomotor activity rhythm were calculated. The results show that 5-HTP differentially shifts the phase of the rhythm, causing phase advances from CT 0 to CT 12 and phase delays from CT 12 to CT 21. Maximum advance phase shift was at CT 6 (1.18 ± 0.37 h) and maximum delay was at CT 18 (−2.36 ± 0.56 h). No extended dead zone is apparent. Vehicle (saline) at any CT did not evoke a significant phase shift. Investigations with different doses (10, 50, 100, and 200 mg/kg) of 5-HTP revealed that the phase resetting effect is dose-dependent. The shape of the phase–response curve (PRC) has a strong similarity to PRCs obtained using some serotonergic agents. There was no significant increase in wheel-running activity after 5-HTP injection, ruling out behavioral arousal-dependent shifts. This suggests that this phase resetting does not completely depend on feedback of the overt rhythmic behavior on the circadian clock. A mechanistic explanation of these shifts is currently lacking.
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References
Amer A, Breu J, McDermott J, Wurtman RJ, Maher TJ (2004) 5-hydroxy-l-tryptophan suppresses food intake in food-deprived and stressed rats. Pharmacol Biochem Behav 77:137–143. doi:10.1016/j.pbb.2003.10.011
Antle MC, Ogilvie MD, Pickard GE, Mistlberger RE (2003) Response of the mouse circadian system to serotonin 1A/2/7 agonists in vivo: surprisingly little. J Biol Rhythm 18:145–158. doi:10.1177/0748730403251805
Aplin KP, Brown PB, Jacob J, Krebs CJ, Singleton GR (2003) Field methods for rodent studies in Asia and the Indo-Pacific. ACIAR Monograph No. 100: 121–191. http://aciar.gov.au/publication/MN100. Accessed 10 February 2011
Arai R, Karasawa N, Nagatsu T, Nagatsu I (1995) Exogenous l-5-hydroxytryptophan is decarboxylated in neurons of the substantia nigra pars compacta and locus coeruleus of the rat. Brain Res 669:145–149. doi:10.1016/0006-8993(94)01259-K
Bardhan A, Sharma T (2000) Meiosis and speciation: a study in a speciating Mus terricolor complex. J Genet 79:105–111. doi:10.1007/BF02715858
Bartoszewicz R, Barbacka-Surowiak G (2010) The phase shift of locomotor activity rhythm after application of 8-OH-DPAT under constant light in mice. Biol Rhythm Res 41:49–56. doi:10.1080/09291010802568723
Bartoszewicz R, Chmielewska D, Domon M, Barbacka-Surowiak G (2010) Influence of short-term constant light on phase shift of mouse circadian locomotor activity rhythm induced by agonist and antagonist of serotonin. Biol Rhythm Res 41:279–288. doi:10.1080/09291010903018016
Birdsall TC (1998) 5-hydroxytryptophan: a clinically-effective serotonin precursor. Alternative Med Rev 3:271–280
Bobrzynska KJ, Godfrey MH, Mrosovsky N (1996) Serotonergic stimulation and nonphotic phase-shifting in hamsters. Physiol Behav 59:221–230. doi:10.1016/0031-9384(95)02130-2
Chidambaram R, Marimuthu G, Sharma VK (2004) Effects of behavioural feedback on the circadian clocks of the nocturnal field mouse Mus booduga. Biol Rhythm Res 35:213–227. doi:10.1080/09291010412331335760
Čičin-Šain L, Jernej B (1996) Reduction of gastrointestinal serotonin in alloxan-diabetic rats: reversal by 5-hydroxytryptophan treatment. Behav Brain Res 73:285–288
Croonenberghs J, Verkerk R, Scharpe S, Deboutte D, Maes M (2005) Serotonergic disturbances in autistic disorder: l-5-hydroxytryptophan administration to autistic youngsters increases the blood concentrations of serotonin in patients but not in controls. Life Sci 76:2171–2183. doi:10.1016/j.lfs.2004.06.032
Croonenberghs J, Wauters A, Deboutte D, Verkerk R, Scharpe S, Maes M (2007) Central serotonergic hypofunction in autism: results of the 5-hydroxy-tryptophan challenge test. Neuroendocrinol Lett 28:449–455
Cuesta M, Clesse D, Pevet P, Challet E (2009) New light on the serotonergic paradox in the rat circadian system. J Neurochem 110:231–243. doi:10.1111/j.1471-4159.2009.06128.x
Cutrera RA, Saboureau M, Pevet P (1996) Phase-shifting effect of 8-OH-DPAT, a 5-HT1A/5-HT1B receptor agonist, on locomotor activity in golden hamster in constant darkness. Neurosci Lett 210:1–4. doi:10.1016/0304-3940(96)12655-0
Ehlen JC, Grossman GH, Glass JD (2001) In vivo resetting of the hamster circadian clock by 5-HT7 receptors in the suprachiasmatic nucleus. J Neurosci 21:5351–5357
Haldar C, Saxena N (1988) Pineal gland and humidity effects on testicular function of the Indian palm squirrel, Funambulus pennanti. J Pineal Res 5:411–418. doi:10.1111/j.1600-079X.1988.tb00784.x
Handley SL (1995) 5-hydroxytryptamine pathways in anxiety and its treatment. Pharmacol Ther 66:103–148. doi:10.1016/0163-7258(95)00004-Z
Hayashi Y, Jacob-Vadakot S, Dugan EA, McBride S, Olexa R, Simansky K, Murray M, Shumsky JS (2010) 5-HT precursor loading, but not 5-HT receptor agonists, increases motor function after spinal cord contusion in adult rats. Exp Neurol 221:68–78. doi:10.1016/j.expneurol.2009.10.003
Horikawa K, Yokota S, Fuji K, Akiyama M, Moriya T, Okamura H, Shibata S (2000) Nonphotic entrainment by 5-HT1A/7 receptor agonists accompanied by reduced Per1 and Per2 mRNA levels in the suprachiasmatic nuclei. J Neurosci 20:5867–5873
Imeri L, Mancia M, Bianchi M, Opp MR (2000) 5-hydroxytryptophan, but not l-tryptophan, alters sleep and brain temperature in rats. Neuroscience 95:445–452. doi:10.1016/S0306-4522(99)00435-2
Joyce D, Mrosovsky N (1964) Eating, drinking and activity in rats following 5-hydroxytryptophan (5-HTP) administration. Psychopharmacol 5:417–423. doi:10.1007/BF02193478
Jud C, Schmutz I, Hampp G, Oster H, Albrecht U (2005) A guideline for analyzing circadian wheel-running behavior in rodents under different lighting conditions. Biol Proced Online 7:101–116. doi:10.1251/bpo109
Kitahama K, Jouvet A, Fujimiya M, Nagatsu I, Arai R (2002) 5-hydroxytryptophan (5-HTP) uptake and decarboxylation in the kitten brain. J Neural Transm 109:683–689. doi:10.1007/s007020200057
Lall GS, Harrington ME (2006) Potentiation of the resetting effects of light on circadian rhythms of hamsters using serotonin and neuropeptide Y receptor antagonists. Neuroscience 141:1545–1552. doi:10.1016/j.neuroscience.2006.04.029
Lindner K, Hartvig P, Bjurling P, Fasth K, Westerberg G, Långström B (1997) Determination of 5-hydroxy-l-[β-11C]tryptophan and its in vivo-formed radiolabeled metabolites in brain tissue using high-performance liquid chromatography: a study supporting radiotracer kinetics obtained with positron emission tomography. Nucl Med Biol 24:733–738. doi:10.1016/S0969-8051(97)00114-5
Lynn-Bullock CP, Welshhans K, Pallas SL, Katz PS (2004) The effect of oral 5-HTP administration on 5-HTP and 5-HT immunoreactivity in monoaminergic brain regions of rats. J Chem Neuroanat 27:129–138. doi:10.1016/j.jchemneu.2004.02.003
Marshall AT (2004) 5-HTP composition. International Application No. PCT/US2004/010391 (patent). http://www.sumobrain.com/patents/wipo/5-htp-composition/WO2004089298.html. Accessed 10 February 2011
Mintz EM, Gillespie CF, Marvel CL, Huhman KL, Albers HE (1997) Serotonergic regulation of circadian rhythms in Syrian hamsters. Neuroscience 79:563–569. doi:10.1016/S0306-4522(96), 00696-3
Morilo CS, Wolinsky TD (2007) 5-HTP combination therapy. US patent application no. 20070117844. http://www.freepatentsonline.com/y2007/0117844.html. Accessed 10 February 2011
Morris LG, Tate BA (2007) Phase response curve to melatonin in a putatively diurnal rodent, Octodon degus. Chronobiol Int 24:407–411. doi:10.1080/07420520701420352
Morrow JD, Vikraman S, Imeri L, Opp MR (2008) Effects of serotonergic activation by 5-hydroxytryptophan on sleep and body temperature of C57Bl/6J and interleukin-6-deficient mice are dose and time related. Sleep 31:21–33
Nakatani Y, Sato-Suzuki I, Tsujino N, Nakasato A, Seki Y, Fumoto M, Arita H (2008) Augmented brain 5-HT crosses the blood–brain barrier through the 5-HT transporter in rat. Eur J Neurosci 27:2466–2472. doi:10.1111/j.1460-9568.2008.06201.x
Portaluppi F, Touitou Y, Smolensky MH (2008) Ethical and methodological standards for laboratory and medical biological rhythm research. Chronobiol Int 25:999–1016. doi:10.1080/07420520802544530
Prosser RA (2003) Serotonin phase-shifts the mouse suprachiasmatic circadian clock in vitro. Brain Res 966:110–115. doi:10.1016/S0006-8993(02)04206-3
Prosser RA, Miller JD, Heller HC (1990) A serotonin agonist phase-shifts the circadian clock in the suprachiasmatic nuclei in vitro. Brain Res 534:336–339
Prosser RA, Dean RR, Edgar DM, Heller HC, Miller JD (1993) Serotonin and the mammalian circadian system: I. In vitro phase shifts by serotonergic agonists and antagonists. J Biol Rhythm 8:1–16. doi:10.1177/074873049300800101
Prosser RA, Heller HC, Miller JD (1994) Serotonergic phase advances of the mammalian circadian clock involve protein kinase A and K+ channel opening. Brain Res 644:67–73. doi:10.1016/0006-993(94)90348-4
Sharma T (1996) Chromosomal and molecular divergence in the Indian pygmy field mice Mus booduga-terricolor lineage of the subgenus Mus. Genetica 97:331–338. doi:10.1007/BF00055319
Sharma VK, Singaravel M, Subbaraj R, Chandrashekaran MK (1999a) Locomotion activity rhythm in the field mouse Mus booduga phase-shifts to melatonin injections in a dose-dependent manner. Biol Rhythm Res 30:313–320. doi:10.1076/brhm.30.3.313.3047
Sharma VK, Singaravel M, Subbaraj R, Chandrashekaran MK (1999b) Timely administration of melatonin accelerates re-entrainment to phase shifted light–dark cycles in the field mouse Mus booduga. Chronobiol Int 16:163–170. doi:10.3109/07420529909019083
Singh S, Cheong N, Narayan G, Sharma T (2009) Burrow characteristics of the co-existing sibling species Mus booduga and Mus terricolor and the genetic basis of adaptation to hypoxic/hypercapnic stress. BMC Ecol 9:6. doi:10.1186/1472-6785-9-6
Stamford JA, Kruk ZL, Millar J (1990) Striatal dopamine terminals release serotonin after 5-HTP pretreatment: in vivo voltammetric data. Brain Res 515:173–180. doi:10.1016/0006-8993(90)90593-Z
Thorré K, Sarre S, Twahirwa E, Meeusen R, Ebinger G, Haemers A, Michotte Y (1996) Effect of l-tryptophan, l-5-hydroxytryptophan and l-tryptophan prodrugs on the extracellular levels of 5-HT and 5-HIAA in the hippocampus of the rat using microdialysis. Eur J Pharm Sci 4:247–256. doi:10.1016/0928-0987(95)00056-9
Tiwari AC, Kumar P, Singh S, Sharma D, Chaturvedi CM (2006) Reproductive phase-dependent circadian variation in hypothalamic concentration of serotonin, dopamine and peripheral thyroxine levels in Japanese Quail following 5-HTP and l-DOPA administration at specific time intervals. Biol Rhythm Res 37:73–86. doi:10.1080/09291010500239684
Tomioka K (1999) Light and serotonin phase-shift the circadian clock in the cricket optic lobe in vitro. J Comp Physiol A 185:437–444. doi:10.1007/s003590050404
Touret M, Sarda N, Gharib A, Geffard M, Jouvet M (1991) The role of 5-hydroxytryptophan (5-HTP) in the regulation of the sleep/wake cycle in parachlorophenylalanine (p-CPA) pretreated rat: a multiple approach study. Exp Brain Res 86:117–124. doi:10.1007/BF00231046
Turner EH, Loftis JM, Blackwell AD (2006) Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. Pharmacol Therapeut 109:325–338. doi:10.1016/j.pharmthera.2005.06.004
Westenberg HGM, den Boer JA (1989) Serotonin functions in panic disorder: effect of l-5-hydroxytryptophan in patient and controls. Psychopharmacol 98:283–285. doi:10.1007/BF00444706
Yuan Q, Lin F, Zheng X, Sehgal A (2005) Serotonin modulates circadian entrainment in Drosophila. Neuron 47:115–127. doi:10.1016/j.neuron.2005.05.027
Acknowledgements
Financial aid to MS by Banaras Hindu University vide grant no. (F (A) 1-14(G)/3449) and University Grants Commission (Junior and Senior Research Fellowship grant to PB) are highly acknowledged. The authors are thankful to Mr. Punit Kumar for his help with animal handling and maintenance.
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Basu, P., Singaravel, M. & Haldar, C. l-5-hydroxytryptophan resets the circadian locomotor activity rhythm of the nocturnal Indian pygmy field mouse, Mus terricolor . Naturwissenschaften 99, 233–239 (2012). https://doi.org/10.1007/s00114-012-0893-5
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DOI: https://doi.org/10.1007/s00114-012-0893-5