Less morphine recall if preceded by twice a week Vitamin D (400 IU per kg in rats, human weights 80 kg) – Aug 2023

Attenuation of morphine conditioned place preference and reinstatement by vitamin D

Behav Pharmacol. 2023 Aug 15. doi: 10.1097/FBP.0000000000000747
Mahdieh Akbari 1, Houman Parsaei 2, Katayoun Sedaghat 1, Fatemeh Mousavi 1

• 1 Research Center of Physiology, Semnan University of Medical Sciences, Semnan and.
• 2 Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Opioid action in the brain involves the dopamine-reward system as well as non-dopamine pathways. Since vitamin D also modulates the brain's dopamine system, the question of this study was how vitamin D might affect the opioid influences on the reward system. Therefore, the objective of this study was to investigate the possible effect of vitamin D on the conditioned place preference (CPP) induced by morphine, as a valuable model of assessment of the reinforcing properties of opioids by associating the context to the rewarding properties of the addictive drugs. Male Wistar rats were randomly divided into two main groups that either received saline (morphine vehicle) or morphine (5 mg/kg, intraperitoneally) for CPP. Each of the main groups was divided into three vitamin D treatment subgroups: vitamin D vehicle and vitamin D (5 and 10 μg/kg, intraperitoneally). Vitamin D injections were started 1 week ahead of the experiment (two injections) or immediately after post-conditioning and in both cases, it was continued twice weekly throughout the CPP. Administration of vitamin D (10 μg/kg) before conditioning in CPP markedly attenuated morphine expression in the post-conditioning test. Receiving vitamin D (5 or 10 μg/kg) before or after conditioning significantly attenuated morphine reinstatement. Administration of vitamin D after opioid conditioning facilitated morphine memory extinction and attenuated morphine reinstatement. Vitamin D is probably a valuable addition to be considered as a part of the treatment for prevention or minimizing the dependency or relapse to opioids.

32 References

1. Abdel-Zaher AO, Mostafa MG, Farghly HM, Hamdy MM, Omran GA, Al-Shaibani NK (2013). Inhibition of brain oxidative stress and inducible nitric oxide synthase expression by thymoquinone attenuates the development of morphine tolerance and dependence in mice. Eur J Pharmacol 702:62–70.
2. Al-Amin MM, Sullivan RKP, Alexander S, Carter DA, Bradford D, Burne THJ (2022). Impaired spatial memory in adult vitamin D deficient BALB/c mice is associated with reductions in spine density, nitric oxide, and neural nitric oxide synthase in the hippocampus. AIMS Neurosci 9:31–56.
3. Alvandi MS, Bourmpoula M, Homberg JR, Fathollahi Y (2017). Association of contextual cues with morphine reward increases neural and synaptic plasticity in the ventral hippocampus of rats. Addict Biol 22:1883–1894.
4. Badiani A, Belin D, Epstein D, Calu D, Shaham Y (2011). Opiate versus psychostimulant addiction: the differences do matter. Nat Rev Neurosci 12:685–700.
5. Cui X, Pelekanos M, Liu PY, Burne TH, McGrath JJ, Eyles DW (2013). The vitamin D receptor in dopamine neurons; its presence in human substantia nigra and its ontogenesis in rat midbrain. Neuroscience 236:77–87.
6. Cui X, McGrath JJ, Burne THJ, Eyles DW (2021). Vitamin D and schizophrenia: 20 years on. Mol Psychiatry 26:2708–2720.
7. Eserian JK (2013). Vitamin D as an effective treatment approach for drug abuse and addiction. Iran J Med Hypo Ideas 7:35–39.
8. Eyles DW, Smith S, Kinobe R, Hewison M, McGrath JJ (2005). Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat 29:21–30.
9. Fakira AK, Massaly N, Cohensedgh O, Berman A, Morón JA (2016). morphine-associated contextual cues induce structural plasticity in hippocampal CA1 pyramidal neurons. Neuropsychopharmacology 41:2668–2678.
10. Gáll Z, Székely O (2021). Role of vitamin D in cognitive dysfunction: new molecular concepts and discrepancies between animal and human findings. Nutrients 13:3672.
11. Kemény LV, Robinson KC, Hermann AL, Walker DM, Regan S, Yew YW, et al. (2021). Vitamin D deficiency exacerbates UV/endorphin and opioid addiction. Sci Adv 7:7.
12. Khaleghzadeh-Ahangar H, Haghparast A (2015). Intra-accumbal CB1 receptor blockade reduced extinction and reinstatement of morphine. Physiol Behav 149:212–219.
13. Kim J, Ham S, Hong H, Moon C, Im HI (2016). Brain reward circuits in morphine addiction. Mol Cells 39:645–653.
14. Kim Y, Zhang F, Su K, LaRochelle M, Callahan M, Fisher D, et al. 2020a). Perioperative serum 25-hydroxyvitamin D levels as a predictor of postoperative opioid use and opioid use disorder: a cohort study. J Gen Intern Med 35:2545–2552.
15. Kim HA, Perrelli A, Ragni A, Retta F, De Silva TM, Sobey CG, et al. 2020b). Vitamin D deficiency and the risk of cerebrovascular disease. Antioxidants (Basel) 9:327.
16. Landel V, Annweiler C, Millet P, Morello M, Féron F (2016). Vitamin D, cognition and Alzheimer’s disease: the therapeutic benefit is in the D-tails. J Alzheimers Dis 53:419–444.
17. Lardner AL (2015). Vitamin D and hippocampal development—the story so far. Front Mol Neurosci 8:58.
18. Latimer CS, Brewer LD, Searcy JL, Chen KC, Popovic J, Kraner SD, et al. (2014). Vitamin D prevents cognitive decline and enhances hippocampal synaptic function in aging rats. Proc Natl Acad Sci USA 111:E4359–E4366.
19. Liang J, Ma SS, Li YJ, Ping XJ, Hu L, Cui CL (2012). Dynamic changes of tyrosine hydroxylase and dopamine concentrations in the ventral tegmental area-nucleus accumbens projection during the expression of morphine-induced conditioned place preference in rats. Neurochem Res 37:1482–1489.
20. Liang Q, Cai C, Duan D, Hu X, Hua W, Jiang P, et al. (2018). Postnatal vitamin D intake modulates hippocampal learning and memory in adult mice. Front Neurosci 12:141.
21. Liu H, He Y, Beck J, da Silva Teixeira S, Harrison K, Xu Y, et al. (2021). Defining vitamin D receptor expression in the brain using a novel VDR(Cre) mouse. J Comp Neurol 529:2362–2375.
22. Lu L, Su WJ, Yue W, Ge X, Su F, Pei G, et al. (2001). Attenuation of morphine dependence and withdrawal in rats by venlafaxine, a serotonin and noradrenaline reuptake inhibitor. Life Sci 69:37–46.
23. McDevitt DS, Jonik B, Graziane NM (2019). morphine differentially alters the synaptic and intrinsic properties of D1R- and D2R-expressing medium spiny neurons in the nucleus accumbens. Front Synaptic Neurosci 11:35.
24. Oliver RJ (2021). Potential involvement of a substantia nigra circuit in opioid reinforcement. J Neurosci 41:4169–4171.
25. Patrick RP, Ames BN (2014). Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism. FASEB J 28:2398–2413.
26. Pertile RA, Cui X, Eyles DW (2016). Vitamin D signaling and the differentiation of developing dopamine systems. Neuroscience 333:193–203.
27. Rivera PD, Raghavan RK, Yun S, Latchney SE, McGovern MK, García EF, et al. (2015). Retrieval of morphine-associated context induces cFos in dentate gyrus neurons. Hippocampus 25:409–414.
28. Sedaghat K, Yousefian Z, Vafaei AA, Rashidy-Pour A, Parsaei H, Khaleghian A, et al. (2019). Mesolimbic dopamine system and its modulation by vitamin D in a chronic mild stress model of depression in the rat. Behav Brain Res 356:156–169.
29. Sedaghat K, Naderian R, Pakdel R, Bandegi AR, Ghods Z (2021). Regulatory effect of vitamin D on pro-inflammatory cytokines and anti-oxidative enzymes dysregulations due to chronic mild stress in the rat hippocampus and prefrontal cortical area. Mol Biol Rep 48:7865–7873.
30. Simantov R (1993). Chronic morphine alters dopamine transporter density in the rat brain: possible role in the mechanism of drug addiction. Neurosci Lett 163:121–124.
31. Spielewoy C, Gonon F, Roubert C, Fauchey V, Jaber M, Caron MG, et al. (2000). Increased rewarding properties of morphine in dopamine-transporter knockout mice. Eur J Neurosci 12:1827–1837.
32. Trinko JR, Land BB, Solecki WB, Wickham RJ, Tellez LA, Maldonado-Aviles J, et al. (2016). Vitamin D3: a role in dopamine circuit regulation, diet-induced obesity, and drug consumption. eNeuro 3:ENEURO.0122–15.2016.
33. Zeng XS, Geng WS, Wang ZQ, Jia JJ (2020). morphine addiction and oxidative stress: the potential effects of thioredoxin-1. Front Pharmacol 11:82.

16+ Vitamin D Life pages have MORPHINE or OPIOIDS or OPIATE or ADDICTION in the title

This list is automatically updated

40,500 hits for (morphine OR opioids OR opiates OR addiction) "vitamin D" in Google Scholar Dec 2023

• The effect of vitamin D on morphine preference in rats: Possible biochemical and DRD2–GDNF signaling - Jan 2023 https://doi.org/10.1002/brb3.2877 FREE PDF
• Putative role of vitamin D in the mechanism of alcoholism and other addictions – a hypothesis - Feb 2021 https://doi.org/10.1017/neu.2020.41 FREE PDF
  • 5 studies, VDR and other genes can restrict Vitamin D from getting to brain cells
• Vitamin D and Its Potential Interplay With Pain Signaling Pathways - May 2020 https://doi.org/10.3389/fimmu.2020.00820 FREE PDF
• Does vitamin D supplementation decrease opioid use in patients with cancer? - Feb 2022. https://doi.org/10.1097/EBP.0000000000001536
• ‘Palliative-D’—Vitamin D Supplementation to Palliative Cancer Patients: A Double Blind, Randomized Placebo-Controlled Multicenter Trial - July 2021 https://doi.org/10.3390/cancers13153707 FREE PDF

Vitamin D Life – Pain - chronic category has:

See also

• Overview Pain and Vitamin D
• Percentage of people with pain increased 25 percent in 18 years – Jan 2019
• Pain not reduced by 60,000 IU monthly vitamin D (need 50,000 IU weekly) – RCT Aug 2023
• Overview Fibromyalgia or Chronic Fatigue and vitamin D
• Overview Rheumatoid Arthritis and vitamin D
• Shingles and vitamin D
• Shin splints decrease with vitamin D
• Migraine and Vitamin D
• Headache category 79 items
• "musculoskeletal pain" 490 items as of Aug 2023
• "chronic fatigue" 185 items as of Jan 2017
• Category Back Pain 42 items
• 7 pain studies in Vitamin D Life with KNEE in the title as of Aug 2023 (see below)
• Opioid OR Opiate OR Morphine in the title 10 pages as of June 2021

Wikipedia description of Conditioned place preference

"Conditioned place preference (CPP) is a form of Pavlovian conditioning used to measure the motivational effects of objects or experiences. This motivation comes from the pleasurable aspect of the experience, so that the brain can be reminded of the context that surrounded the "encounter". By measuring the amount of time an animal spends in an area that has been associated with a stimulus, researchers can infer the animal's liking for the stimulus."