Skip to main content
Log in

Sucrose intake by rats affected by both intraperitoneal oxytocin administration and time of day

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Daily limited access to palatable food or drink at a fixed time is commonly used in rodent models of bingeing. Under these conditions, entrainment may modulate intake patterns. Oxytocin is involved in circadian patterns of intake and, when administered peripherally, reduces sucrose intake. However, oxytocin’s effects on intake under limited-access conditions and its potential interaction with entrainment have not been explored.

Objectives

This study examined the role of entrainment on intake patterns, oxytocin’s effects on sucrose intakes and locomotor activity and whether oxytocin’s effects were mediated by its actions at the oxytocin receptor.

Methods

Sated rats received daily 1-h access to 10% sucrose solution either at a fixed or varied time of day. Rats received intraperitoneal oxytocin (0 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg) prior to sucrose access, and spontaneous locomotor activity was assessed in an open-field test. Rats were then pre-treated with an oxytocin receptor antagonist, L368,899, prior to oxytocin before sucrose access.

Results

Intake patterns did not differ between fixed- or varied-time presentations; rats consumed more sucrose solution in the middle as opposed to the early-dark phase. Oxytocin dose-dependently reduced sucrose intakes, but also reduced locomotor activity. There was some evidence of partial blockade of oxytocin-induced sucrose intake reductions by L368,899, but the results were unclear.

Conclusions

Time of day and oxytocin impact sucrose solution intake under daily limited access in rats and the sedative-like effects of oxytocin should be considered in future studies on oxytocin and food intake.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Abe H, Rusak B (1992) Anticipatory activity and entrainment of circadian rhythms in Syrian hamsters exposed to restricted palatable diets. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 263(1 Pt 2):R116-124. https://doi.org/10.1152/ajpregu.1992.263.1.R116

    Article  CAS  Google Scholar 

  • Agabio R, Farci AMG, Curreli O, Deidda R, Mercuro S, Naitana R, . . . Melis MR (2016). Oxytocin nasal spray in the treatment of binge eating disorder and obesity: a pilot, randomized, double blind trial

  • Angeles-Castellanos M, Salgado-Delgado R, Rodriguez K, Buijs R, Escobar C (2008) Expectancy for food or expectancy for chocolate reveals timing systems for metabolism and reward. Neuroscience 155(1):297–307

    CAS  PubMed  Google Scholar 

  • Arletti R, Benelli A, Bertolini A (1990) Oxytocin inhibits food and fluid intake in rats. Physiology & Behavior, 48(6):825–830

    CAS  Google Scholar 

  • Bake T, Morgan D, Mercer JG (2014a) Feeding and metabolic consequences of scheduled consumption of large, binge-type meals of high fat diet in the Sprague-Dawley rat. Physiology & Behavior, 128:70–79

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bake T, Murphy M, Morgan DGA, Mercer JG (2014b) Large, binge-type meals of high fat diet change feeding behaviour and entrain food anticipatory activity in mice. Appetite 77:62–73

    PubMed Central  Google Scholar 

  • Benelli A, Bertolini A, Arletti R (1991) Oxytocin-induced inhibition of feeding and drinking: no sexual dimorphism in rats. Neuropeptides 20(1):57–62

    CAS  PubMed  Google Scholar 

  • Berner LA, Avena NM, Hoebel BG (2008) Bingeing, self-restriction, and increased body weight in rats with limited access to a sweet-fat diet. Obesity 16(9):1998–2002

    CAS  PubMed  Google Scholar 

  • Berridge KC, Robinson TE (2016) Liking, wanting, and the incentive-sensitization theory of addiction. American Psychologist, 71(8):670

    Google Scholar 

  • Boakes RA, & Wu J (2020). Time-of-day affects the amount rats run during daily sessions in activity wheels. Learning & Behavior, 1–8

  • Bolles RC, Moot SA (1973) The rat’s anticipation of two meals a day. Journal of Comparative and Physiological Psychology, 83(3):510

    CAS  PubMed  Google Scholar 

  • Boulos Z, Rosenwasser AM, Terman M (1980) Feeding schedules and the circadian organization of behavior in the rat. Behavioral Brain Research, 1(1):39–65

    CAS  Google Scholar 

  • Bowen MT, McGregor IS (2014) Oxytocin and vasopressin modulate the social response to threat: a preclinical study. International Journal of Neuropsychopharmacology, 17(10):1621–1633

    CAS  Google Scholar 

  • Bowen MT, Neumann ID (2017) Rebalancing the addicted brain: oxytocin interference with the neural substrates of addiction. Trends in Neurosciences, 40(12):691–708

    CAS  PubMed  Google Scholar 

  • Bowen MT (2019). Does peripherally administered oxytocin enter the brain? Compelling new evidence in a long-running debate. Pharmacological Research 146:104325. doi: 10.1016/j.phrs.2019.104325.

  • Brennan K, Roberts D, Anisman H, Merali Z (2001) Individual differences in sucrose consumption in the rat: motivational and neurochemical correlates of hedonia. Psychopharmacology 157(3):269–276

    CAS  PubMed  Google Scholar 

  • Caba M, Huerta C, Meza E, Hernández M, & Rovirosa-Hernández MJ (2020). Oxytocinergic cells of the hypothalamic paraventricular nucleus are involved in food entrainment. Frontiers in Neuroscience, 14.

  • Edmonds SC, Adler NT (1977) Food and light as entrainers of circadian running activity in the rat. Physiology & Behavior, 18(5):915–919

    CAS  Google Scholar 

  • Everett NA, McGregor IS, Baracz SJ, Cornish JL (2018) The role of the vasopressin V1A receptor in oxytocin modulation of methamphetamine primed reinstatement. Neuropharmacology 133:1–11

    CAS  PubMed  Google Scholar 

  • Everett NA, Carey HA, Cornish JL, Baracz SJ (2020) Sign tracking predicts cue-induced but not drug-primed reinstatement to methamphetamine seeking in rats: effects of oxytocin treatment. Psychopharmacology 34(11):1271–1279

    PubMed  Google Scholar 

  • Furlong TM, Jayaweera HK, Balleine BW, Corbit LH (2014) Binge-like consumption of a palatable food accelerates habitual control of behavior and is dependent on activation of the dorsolateral striatum. Journal of Neuroscience 34(14):5012–5022

    CAS  PubMed  Google Scholar 

  • Gulati K, Ray A, Sharma KK (1991) Effects of acute and chronic morphine on food intake in rats: modulation by oxytocin and vasopressin. Pharmacology Biochemistry and Behavior 40(1):27–32

    CAS  PubMed  Google Scholar 

  • Hara E, Saito M (1989) Diurnal change in digestion and absorption of sucrose in vivo in rats. Journal of nutritional science and vitaminology, 35(6):667–671

    CAS  PubMed  Google Scholar 

  • Hardaway JA, Jensen J, Kim M, Mazzone CM, Sugam JA, Diberto JF, . . . Kash TL (2016). Nociceptin receptor antagonist SB 612111 decreases high fat diet binge eating. Behavioural Brain Research, 307, 25-34

  • Herisson F, Waas J, Fredriksson R, Schiöth HB, Levine AS, & Olszewski P (2016). Oxytocin acting in the nucleus accumbens core decreases food intake. Journal of Neuroendocrinology, 28(4)

  • Ho JM, Anekonda VT, Thompson BW, Zhu M, Curry RW, Hwang BH, . . . Appleyard SM (2014). Hindbrain oxytocin receptors contribute to the effects of circulating oxytocin on food intake in male rats. Endocrinology, 155(8), 2845-2857

  • Inouye S-I, Kawamura H (1979) Persistence of circadian rhythmicity in a mammalian hypothalamic “island” containing the suprachiasmatic nucleus. Proc Natl Acad Sci 76(11):5962–5966

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kersten A, Strubbe JH, Spiteri NJ (1980) Meal patterning of rats with changes in day length and food availability. Physiology & Behavior 25(6):953–958

    CAS  Google Scholar 

  • Kinzig KP, Hargrave SL, Honors MA (2008) Binge-type eating attenuates corticosterone and hypophagic responses to restraint stress. Physiology & Behavior, 95(1):108–113

    CAS  Google Scholar 

  • Klenerova V, Krejci I, Sida P, Hlinak Z, Hynie S (2009) Oxytocin and carbetocin effects on spontaneous behavior of male rats: modulation by oxytocin receptor antagonists. Neuroendocrinology Letters, 30:335–342

    CAS  PubMed  Google Scholar 

  • Klockars A, Brunton C, Li L, Levine AS, Olszewski PK (2017) Intravenous administration of oxytocin in rats acutely decreases deprivation-induced chow intake, but it fails to affect consumption of palatable solutions. Peptides 93:13–19

    CAS  PubMed  Google Scholar 

  • Kosheleff AR, Araki J, Hsueh J, Le A, Quizon K, Ostlund SB, . . . Murphy NP (2018). Pattern of access determines influence of junk food diet on cue sensitivity and palatability. Appetite, 123, 135-145

  • Lee S-Y, Park S-H, Chung C, Kim JJ, Choi S-Y, Han J-S (2015) Oxytocin protects hippocampal memory and plasticity from uncontrollable stress. Scientific Reports, 5:18540

    CAS  PubMed  PubMed Central  Google Scholar 

  • Leslie M, Silva P, Paloyelis Y, Blevins J, Treasure J (2018) A systematic review and quantitative meta-analysis of the effects of oxytocin on feeding. Journal of Neuroendocrinology, 30(8):e12584. https://doi.org/10.1111/jne.12584

    Article  CAS  Google Scholar 

  • Leslie M, Leppanen J, Paloyelis Y, Treasure J (2020) A pilot study investigating the influence of oxytocin on attentional bias to food images in women with bulimia nervosa or binge eating disorder. Journal of Neuroendocrinology 32(5):e12843

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lin C-H, Tsai C-C, Chen T-H, Chang C-P, Yang H-H (2019) Oxytocin maintains lung histological and functional integrity to confer protection in heat stroke. Scientific Reports, 9(1):1–10

    Google Scholar 

  • Maejima Y, Sakuma K, Santoso P, Gantulga D, Katsurada K, Ueta Y, . . . Shimomura K (2014). Oxytocinergic circuit from paraventricular and supraoptic nuclei to arcuate POMC neurons in hypothalamus. FEBS letters, 588(23), 4404-4412

  • Manning M, Misicka A, Olma A, Bankowski K, Stoev S, Chini B, . . . Guillon G (2012). Oxytocin and vasopressin agonists and antagonists as research tools and potential therapeutics. Journal of Neuroendocrinology, 24(4), 609-628

  • Mendoza J, Angeles-Castellanos M, Escobar C (2005) Entrainment by a palatable meal induces food-anticipatory activity and c-Fos expression in reward-related areas of the brain. Neuroscience 133(1):293–303

    CAS  PubMed  Google Scholar 

  • Mens WB, Witter A, Greidanus TBVW (1983) Penetration of neurohypophyseal hormones from plasma into cerebrospinal fluid (CSF): half-times of disappearance of these neuropeptides from CSF. Brain Research, 262(1):143–149

    CAS  PubMed  Google Scholar 

  • Mistlberger RE (1993) Effects of scheduled food and water access on circadian rhythms of hamsters in constant light, dark, and light: dark. Physiology & Behavior, 53(3):509–516

    CAS  Google Scholar 

  • Mistlberger RE (1994) Circadian food-anticipatory activity: formal models and physiological mechanisms. Neuroscience & Biobehavioral Reviews, 18(2):171–195

    CAS  Google Scholar 

  • Mistlberger RE (2009) Food anticipatory circadian rhythms: concepts and methods. European Journal of Neuroscience, 30(9):1718–1729

    Google Scholar 

  • Mistlberger RE, Rusak B (1987) Palatable daily meals entrain anticipatory activity rhythms in free-feeding rats: dependence on meal size and nutrient content. Physiology & Behavior 41(3):219–226

    CAS  Google Scholar 

  • Mullis K, Kay K, Williams DL (2013) Oxytocin action in the ventral tegmental area affects sucrose intake. Brain Research, 1513:85–91

    CAS  PubMed  PubMed Central  Google Scholar 

  • Muñoz-Escobar G, Guerrero-Vargas NN, Escobar C (2019) Random access to palatable food stimulates similar addiction-like responses as a fixed schedule, but only a fixed schedule elicits anticipatory activation. Scientific Reports, 9(1):1–13

    Google Scholar 

  • Neumann ID, Maloumby R, Beiderbeck DI, Lukas M, Landgraf R (2013) Increased brain and plasma oxytocin after nasal and peripheral administration in rats and mice. Psychoneuroendocrinology 38(10):1985–1993

    CAS  PubMed  Google Scholar 

  • Noble EE, Billington CJ, Kotz CM, Wang C (2014) Oxytocin in the ventromedial hypothalamic nucleus reduces feeding and acutely increases energy expenditure. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 307(6):R737–R745

    CAS  PubMed  PubMed Central  Google Scholar 

  • Olszewski PK, Shaw TJ, Grace MK, Höglund CE, Fredriksson R, Schiöth HB, Levine AS (2009) Complexity of neural mechanisms underlying overconsumption of sugar in scheduled feeding: involvement of opioids, orexin, oxytocin and NPY. Peptides 30(2):226–233

    CAS  PubMed  Google Scholar 

  • Olszewski PK, Klockars A, Olszewska AM, Fredriksson R, Schiöth HB, Levine AS (2010) Molecular, immunohistochemical, and pharmacological evidence of oxytocin’s role as inhibitor of carbohydrate but not fat intake. Endocrinology 151(10):4736–4744. https://doi.org/10.1210/en.2010-0151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Olszewski PK, Allen K, Levine AS (2015) Effect of oxytocin receptor blockade on appetite for sugar is modified by social context. Appetite 86:81–87

    PubMed  Google Scholar 

  • Ong ZY, Alhadeff AL, Grill HJ (2015) Medial nucleus tractus solitarius oxytocin receptor signaling and food intake control: the role of gastrointestinal satiation signal processing. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 308(9):R800–R806

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ramos L, Hicks C, Kevin R, Caminer A, Narlawar R, Kassiou M, McGregor IS (2013) Acute prosocial effects of oxytocin and vasopressin when given alone or in combination with 3, 4-methylenedioxymethamphetamine in rats: involvement of the V1 A receptor. Neuropsychopharmacology 38(11):2249–2259

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rhodes JS, Best K, Belknap JK, Finn DA, Crabbe JC (2005) Evaluation of a simple model of ethanol drinking to intoxication in C57BL/6J mice. Physiology & Behavior 84(1):53–63

    CAS  Google Scholar 

  • Richter CP (1922). A behavioristic study of the activity of the rat. Comparative Psychology Monographs

  • Romano A, Friuli M, Cifani C, & Gaetani S (2020). Oxytocin in the neural control of eating: at the crossroad between homeostatic and non-homeostatic signals. Neuropharmacology, 108082

  • Sabatier N, Leng G, & Menzies J (2013). Oxytocin, feeding, and satiety. Frontiers in Endocrinology, 4(35). doi:https://doi.org/10.3389/fendo.2013.00035

  • Saito R, Sonoda S, Ueno H, Motojima Y, Yoshimura M, Maruyama T, . . . Kusuhara K (2017). Involvement of central nesfatin-1 neurons on oxytocin-induced feeding suppression in rats. Neuroscience Letters, 655, 54-60

  • Sala M, Braida D, Lentini D, Busnelli M, Bulgheroni E, Capurro V, . . . Rubino T (2011). Pharmacologic rescue of impaired cognitive flexibility, social deficits, increased aggression, and seizure susceptibility in oxytocin receptor null mice: a neurobehavioral model of autism. Biological psychiatry, 69(9), 875-882

  • Sclafani A, Rinaman L, Vollmer RR, Amico JA (2007) Oxytocin knockout mice demonstrate enhanced intake of sweet and nonsweet carbohydrate solutions. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 292(5):R1828–R1833

    CAS  PubMed  Google Scholar 

  • Siegal PS (1961) Food intake in the rat in relation to the dark-light cycle. Journal of Comparative and Physiological Psychology 54(3):294

    Google Scholar 

  • Smith AS, Korgan AC, Young WS (2019) Oxytocin delivered nasally or intraperitoneally reaches the brain and plasma of normal and oxytocin knockout mice. Pharmacological Research 146:104324

    CAS  PubMed  PubMed Central  Google Scholar 

  • Spiteri NJ (1982) Circadian patterning of feeding, drinking and activity during diurnal food access in rats. Physiology & Behavior 28(1):139–147

    CAS  Google Scholar 

  • Tan O, Musullulu H, Raymond JS, Wilson B, Langguth M, Bowen MT (2019) Oxytocin and vasopressin inhibit hyper-aggressive behaviour in socially isolated mice. Neuropharmacology, 156:107573

  • Terman M, Terman JS (1975) Control of the rat’s circadian self-stimulation rhythm by light-dark cycles. Physiology & Behavior, 14(6):781–789

    CAS  Google Scholar 

  • Thompson KL, Vincent SH, Miller RR, Colletti AE, Alvaro RF, Wallace MA, . . . Chiu S-HL (1997). Pharmacokinetics and disposition of the oxytocin receptor antagonist L-368,899 in rats and dogs. Drug metabolism and disposition, 25(10), 1113-1118

  • Tõnissaar M, Herm L, Rinken A, Harro J (2006) Individual differences in sucrose intake and preference in the rat: circadian variation and association with dopamine D2 receptor function in striatum and nucleus accumbens. Neuroscience Letters, 403(1–2):119–124

    PubMed  Google Scholar 

  • Zhang G, Cai D (2011) Circadian intervention of obesity development via resting-stage feeding manipulation or oxytocin treatment. American Journal of Physiology-Endocrinology and Metabolism 301(5):E1004–E1012

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou L, Ghee SM, See RE, Reichel CM (2015) Oxytocin differentially affects sucrose taking and seeking in male and female rats. Behavioural Brain Research, 283:184–190

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge Alison Salo, Manuel Menouhos and Vincent Zappala for providing animal husbandry and assistance during the study. We would also like to thank Stacey Gardiner and Marisa Henry for their management of administrative matters in the University of Sydney’s laboratory animal services.

Funding

This work was supported by the University of Sydney Postgraduate Research Support Scheme awarded to Simone Rehn in 2020.

Author information

Authors and Affiliations

Authors

Contributions

SR conceived and designed the present experiments, collected experimental data, performed data analysis and wrote the first draft of the manuscript. JR assisted in the collection of experimental data, aided with data analysis and was involved in reviewing and editing the manuscript. RB and MB were involved in the conceptualisation and the design of the present experiments, provided advice on data analysis and were involved in reviewing and editing the manuscript.

Corresponding author

Correspondence to Simone Rehn.

Ethics declarations

Conflict of interest

MB is listed as an inventor on patents for novel oxytocin-based therapeutics and for therapeutics for eating disorders and is co-founder and chief scientific officer of a company, Kinoxis Therapeutics Pty Ltd, commercialising this technology. The other authors declare they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rehn, S., Raymond, J.S., Boakes, R.A. et al. Sucrose intake by rats affected by both intraperitoneal oxytocin administration and time of day. Psychopharmacology 239, 429–442 (2022). https://doi.org/10.1007/s00213-021-06014-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-021-06014-3

Keywords

Navigation