EC Nutrition

Research Article Volume 19 Issue 1 - 2024

Acute Immobilization Stress-Induced Anxiety and its Impact on Hippocampal 5-HT1A Signaling in Long-Term Coffee-Treated Rats

Sadia Gul1*, Hira Ahmed2, Atia Gohar1, Rushda Afroz2 and Darakhshan Jabeen Haleem2

1Neuroscience Research Laboratory, H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Pakistan

2Neuroscience Research Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Pakistan

*Corresponding Author: Sadia Gul, Neuroscience Research Laboratory, H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Science (ICCBS), University of Karachi, Karachi, Pakistan.
Received: December 04, 2023; Published: December 12, 2023



Caffeine, a legal psychostimulant, present in coffee, plays a significant role in reversing anxiety-like behavior following exposure to stress. The present study aimed to investigate the effect of acute immobilization stress in long-term coffee-treated rats drinking coffee as a sole source of water, altered locomotor activity, and anxiety in rats using behavioral and receptor expression studies. Forty-eight male Albino Wistar rats (180 - 200g) were randomly divided into 3 groups (n = 16); Water-treated; Coffee low-dose (10 mg/mL); and Coffee high-dose (20 mg/mL) rat groups. The animals received their respective coffee treatment for 14 days, while the animals of the control group were on drinking water. On day 14, animals were further subdivided into 3 groups (n = 8); (i) Water-treated unstressed; (ii) Water-treated stressed; (iii) Coffee low-dose (10 mg/mL) unstressed; (iv) Coffee low-dose (10 mg/mL) stressed; (v) Coffee high-dose (20 mg/mL) unstressed; (vi) Coffee high-dose (20 mg/mL) stressed rat groups. On day 16, 24h after the immobilization stress, activities in the open field (OF) and elevated plus maze (EPM) paradigms were used to assess locomotor and anxiety-like behavior, then animals were subjected to decapitation. Another similar group of rats was used for 14 days of coffee treatment. On day 16, 24h after the immobilization stress, all stressed and unstressed groups were decapitated and the brain region hippocampus was isolated to determine the 5-HT1A receptors expression by using qRT-PCR. The results showed that acute immobilization stress in coffee-treated rats exhibited a motor-depressant effect. Anxiety-like behavior was found both in long-term coffee-treated unstressed and stressed rats. The levels of hippocampal 5-HT1A receptors were downregulated in both unstressed and stressed coffee-treated rats compared to respective controls. The present findings showed that acute immobilization stress in long-term coffee-treated rats potentially induced anxiogenic effects by downregulating 5-HT1A signaling in the hippocampus.

 Keywords: Coffee; 5-HT1A Receptor; Anxiety-Like Behavior; Hippocampus; Immobilization Stress

 

  1. Schneiderman Neil., et al. "Stress and health: psychological, behavioral, and biological determinants”. Annual Review of Clinical Psychology 1 (2005): 607-628.
  2. Salleh Mohd Razali. "Life event, stress and illness”. The Malaysian Journal of Medical Sciences: MJMS4 (2008): 9-18.
  3. Haleem Darakhshan J. "Behavioral deficits and exaggerated feedback control over raphe-hippocampal serotonin neurotransmission in restrained rats”. Pharmacological Reports4 (2011): 888-897.
  4. Suvrathan Aparna., et al. "Effects of chronic and acute stress on rat behaviour in the forced-swim test”. Stress 6 (2010): 533-540.
  5. Du Preez Andrea., et al. "Do different types of stress differentially alter behavioural and neurobiological outcomes associated with depression in rodent models? A systematic review”. Frontiers in Neuroendocrinology 61 (2021): 100896.
  6. Nehlig Astrid. "Effects of coffee/caffeine on brain health and disease: What should I tell my patients?”. Practical Neurology2 (2016): 89-95.
  7. Daly JW., et al. "Is caffeine addictive? The most widely used psychoactive substance in the world affects same parts of the brain as cocaine”. Lakartidningen 51-52 (1998): 5878-5883.
  8. Cakir Ozgur Kasimay., et al. "Protective effect of low dose caffeine on psychological stress and cognitive function”. Physiology and Behavior 168 (2017): 1-10.
  9. Acevedo JeanMarie., et al. "Caffeine stimulates locomotor activity in the mammalian spinal cord via adenosine A1 receptor-dopamine D1 receptor interaction and PKA-dependent mechanisms”. Neuropharmacology 101 (2016): 490-505.
  10. Karuppagounder Senthilkumar S., et al. "Caffeine, a natural methylxanthine nutraceutical, exerts dopaminergic neuroprotection”. Neurochemistry International 148 (2021): 105066.
  11. Plumber Noorine., et al. "Stimulant usage by medical students for cognitive enhancement: A systematic review”. Cureus5 (2021): e15163.
  12. Rasaei Behrouz., et al. "The effect of simultaneous consumption of coffee caffeine and sleep deprivation on plasma ghrelin and leptin levels”. International Journal of Nutrition Sciences2 (2019): 88-96.
  13. Magalhães Ricardo., et al. "Habitual coffee drinkers display a distinct pattern of brain functional connectivity”. Molecular Psychiatry11 (2021): 6589-6598.
  14. Pechlivanova Daniela M., et al. "Effect of long-term caffeine administration on depressive-like behavior in rats exposed to chronic unpredictable stress”. Behavioural Pharmacology4 (2012): 339-347.
  15. Powell William H., et al. "The selective 5-HT1A receptor agonist NLX-112 displays anxiolytic-like activity in mice”. Naunyn-Schmiedeberg's Archives of Pharmacology2 (2022): 149-157.
  16. Raghupathi Revathi K and Paul McGonigle. "Differential effects of three acute stressors on the serotonin 5-HT1A receptor system in rat brain”. Neuroendocrinology4 (1997): 246-258.
  17. Kusserow Heike., et al. "Reduced anxiety-related behaviour in transgenic mice overexpressing serotonin1A receptors”. Molecular Brain Research1-2 (2004): 104-116.
  18. Richards Gareth and Andrew Smith. “Caffeine consumption and self-assessed stress, anxiety, and depression in secondary school children”. Journal of Psychopharmacology (Oxford, England) 12 (2015): 1236-1247.
  19. Prajapati Santosh Kumar., et al. "Repeated caffeine administration aggravates post-traumatic stress disorder-like symptoms in rats”. Physiology and Behavior 211 (2019): 112666.
  20. Haque Zeba., et al. "Inhibition of immobilization stress-induced anorexia, behavioral deficits, and plasma corticosterone secretion by injected leptin in rats”. Stress3 (2013): 353-362.
  21. Samad Noreen and Ayesha Saleem. "Administration of Allium cepa bulb attenuates stress-produced anxiety and depression and improves memory in male mice”. Metabolic Brain Disease 33.1 (2018): 271-281.
  22. Pan Yuqin., et al. "The effects of central pro-and anti-inflammatory immune challenges on depressive-like behavior induced by chronic forced swim stress in rats”. Behavioural Brain Research 247 (2013): 232-240.
  23. Noschang Cristie Grazziotin., et al. "Sex-specific differences on caffeine consumption and chronic stress-induced anxiety-like behavior and DNA breaks in the hippocampus”. Pharmacology Biochemistry and Behavior1 (2009): 63-69.
  24. Antoniou Katerina., et al. "A detailed behavioral analysis of the acute motor effects of caffeine in the rat: involvement of adenosine A 1 and A 2A receptors”. Psychopharmacology2 (2005): 154-162.
  25. Chakraborty Prabahan., et al. "Corticosterone after acute stress prevents the delayed effects on the amygdala”. Neuropsychopharmacology 13 (2020): 2139-2146.
  26. Sudakov SK., et al. "Effect of social isolation on behavioral parameters and sensitivity of rats to morphine and caffeine”. Bulletin of Experimental Biology and Medicine 1 (2003): 6-8.
  27. Hernandes Paloma Molina., et al. "Role of 5-HT1A receptors in the ventral hippocampus in the regulation of anxiety-and panic-related defensive behaviors in rats”. Behavioural Brain Research 408 (2021): 113296.
  28. Mineur Yann S., et al. "Expression of the 5-HT1A serotonin receptor in the hippocampus is required for social stress resilience and the antidepressant-like effects induced by the nicotinic partial agonist cytisine”. Neuropsychopharmacology4 (2015): 938-946.

Sadia Gul., et al. “Acute Immobilization Stress-Induced Anxiety and its Impact on Hippocampal 5-HT1A Signaling in Long-Term Coffee-Treated Rats”. EC Nutrition  19.1 (2024): 01-08.