EEffect of Chloroquine on Hyoscine-Induced Memory Impairment in Mice: Possible Involvement of Opioids and Nitric Oxide
-
Parsa Mohammadi
,
Elaheh Karimi
,
Adeleh Maleki
,
Nastaran Rahimi
,
Nahid Fakhraei
,
Saina Saadat Boroujeni
,
Shahabaddin Solaimanian
,
Ahmad Reza Dehpour
Abstract
Accumulating evidence suggests the potential use of chloroquine, an anti-malaria medication, as a neuroprotective agent. Moreover, several studies have reported that the endogenous opioids and nitric oxide (NO) may mediate the chloroquine’s effects. In the present study, effects of chloroquine on hyoscine-induced memory impairment were assessed. Furthermore, the possible involvements of opioids and NO were evaluated. Chloroquine was administered intraperitonially (i.p.) at doses of 0.1, 0.5, 1, 3, 10, and 20 mg/kg to hyoscine-treated (1mg/kg, i.p.) mice, and the spatial and fear memories were evaluated using Y-maze and passive-avoidance tasks, respectively. Also, to provide further evidence about chloroquine’s mechanism of action, the opioid receptors and the NO production were blocked using two nonselective antagonist’s naltrexone and L-NAME, respectively. Chloroquine at doses of 0.5, 10 and 20 mg/kg furtherly damaged the impaired memory of hyoscine-treated mice and at doses of 10 and 20 mg/kg impaired the memory of saline-treated mice in the passive-avoidance task. Additionally, chloroquine at doses of 0.5 and 1 mg/kg improved the spatial memory in hyoscine-treated mice in Y-maze test. In addition, naltrexone (3 mg/kg) reversed the neuroprotective effect of chloroquine (1 mg/kg) in hyoscine-treated mice in Y-maze task. It could be concluded that chloroquine at low doses may improve cognitive performances by involving the opioid receptors; as a result, blocking the opioid receptors may reverse chloroquine’s neuroprotective effect. Notably, chloroquine at high doses did not improve the memory and in combination with hyoscine, it caused even more damage to the long-term memory.
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3. Cheignon, C., et al., Oxidative stress and the amyloid beta peptide in Alzheimer’s disease. Redox biology, 2018. 14: p. 450-464.
4. Gulyaeva, N., et al., Molecular and cellular mechanisms of sporadic Alzheimer’s disease: Studies on rodent models in vivo. Biochemistry (Moscow), 2017. 82(10): p. 1088-1102.
5. Liao, Y., et al., The ameliorating effects of bee pollen on scopolamine-induced cognitive impairment in mice. Biological and Pharmaceutical Bulletin, 2019. 42(3): p. 379-388.
6. Kim, E.-J., et al., Ginsenosides Rg5 and Rh3 protect scopolamine-induced memory deficits in mice. Journal of ethnopharmacology, 2013. 146(1): p. 294-299.
7. Ishola, I.O., et al., Isorhamnetin enhanced cortico-hippocampal learning and memory capability in mice with scopolamine-induced amnesia: role of antioxidant defense, cholinergic and BDNF signaling. Brain Research, 2019. 1712: p. 188-196.
8. Rogers, S., et al., A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Neurology, 1998. 50(1): p. 136-145.
9. Doody, R.S., Refining Treatment Guidelines in Alzheimer's Disease. Geriatrics, 2005.
10. Woster, P.M., New therapies for malaria. 2003.
11. Rainsford, K., et al., Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases. Inflammopharmacology, 2015. 23(5): p. 231-269.
12. Gladman, D., Aspects of use of antimalarials in systemic lupus erythematosus. Journal of rheumatology, 1998. 25(5): p. 983-985.
13. Savarino, A., et al., Effects of chloroquine on viral infections: an old drug against today's diseases. The Lancet infectious diseases, 2003. 3(11): p. 722-727.
14. Maes, H., et al., How to teach an old dog new tricks: autophagy-independent action of chloroquine on the tumor vasculature. Autophagy, 2014. 10(11): p. 2082-2084.
15. Park, J., et al., Chloroquine induces activation of nuclear factor‐κB and subsequent expression of pro‐inflammatory cytokines by human astroglial cells. Journal of neurochemistry, 2003. 84(6): p. 1266-1274.
16. Hirata, Y., et al., Chloroquine inhibits glutamate‐induced death of a neuronal cell line by reducing reactive oxygen species through sigma‐1 receptor. Journal of neurochemistry, 2011. 119(4): p. 839-847.
17. Bartus, R.T., et al., The cholinergic hypothesis of geriatric memory dysfunction. Science, 1982. 217(4558): p. 408-414.
18. Fodale, V., et al., Alzheimer's disease and anaesthesia: implications for the central cholinergic system. BJA: British Journal of Anaesthesia, 2006. 97(4): p. 445-452.
19. Jeong, E.J., et al., Cognitive-enhancing and antioxidant activities of iridoid glycosides from Scrophularia buergeriana in scopolamine-treated mice. European journal of pharmacology, 2008. 588(1): p. 78-84.
20. Ebert, U. and W. Kirch, Scopolamine model of dementia: electroencephalogram findings and cognitive performance. European journal of clinical investigation, 1998. 28(11): p. 944.
21. Traynor, J., μ-Opioid receptors and regulators of G protein signaling (RGS) proteins: from a symposium on new concepts in mu-opioid pharmacology. Drug and alcohol dependence, 2012. 121(3): p. 173-180.
22. Liang, X., et al., Opioid system modulates the immune function: a review. Translational perioperative and pain medicine, 2016. 1(1): p. 5.
23. Onigbogi, O., A. Ajayi, and O. Ukponmwan, Mechanisms of chloroquine-induced body-scratching behavior in rats: evidence of involvement of endogenous opioid peptides. Pharmacology Biochemistry and Behavior, 2000. 65(2): p. 333-337.
24. Torres-Berrio, A. and M.O. Nava-Mesa, The opioid system in stress-induced memory disorders: From basic mechanisms to clinical implications in post-traumatic stress disorder and Alzheimer's disease. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2019. 88: p. 327-338.
25. Cai, Z. and A. Ratka, Opioid system and Alzheimer’s disease. Neuromolecular medicine, 2012. 14(2): p. 91-111.
26. Gallagher, M., Naloxone enhancement of memory processes: Effects of other opiate antagonists. Behavioral and neural biology, 1982. 35(4): p. 375-382.
27. Knowles, R.G. and S. Moncada, Nitric oxide synthases in mammals. Biochemical Journal, 1994. 298(2): p. 249-258.
28. Chen, T.-H., et al., Chloroquine induces the expression of inducible nitric oxide synthase in C6 glioma cells. Pharmacological research, 2005. 51(4): p. 329-336.
29. Böhme, G.A., et al., Possible involvement of nitric oxide in long-term potentiation. European journal of pharmacology, 1991. 199(3): p. 379-381.
30. Prada, J., et al., Upregulation of reactive oxygen and nitrogen intermediates in Plasmodium berghei infected mice after rescue therapy with chloroquine or artemether. Journal of Antimicrobial Chemotherapy, 1996. 38(1): p. 95-102.
31. Moncada, S., The 1991 Ulf von Euler Lecture: The l‐arginine: nitric oxide pathway. Acta physiologica Scandinavica, 1992. 145(3): p. 201-227.
32. Katzoff, A., T. Ben-Gedalya, and A.J. Susswein, Nitric oxide is necessary for multiple memory processes after learning that a food is inedible in Aplysia. Journal of Neuroscience, 2002. 22(21): p. 9581-9594.
33. Bannerman, D., et al., Inhibition of nitric oxide synthase does not impair spatial learning. Journal of Neuroscience, 1994. 14(12): p. 7404-7414.
34. Boultadakis, A., G. Georgiadou, and N. Pitsikas, Effects of the nitric oxide synthase inhibitor L-NAME on different memory components as assessed in the object recognition task in the rat. Behavioural brain research, 2010. 207(1): p. 208-214.
35. Hassanipour, M., et al., Possible involvement of nitrergic and opioidergic systems in the modulatory effect of acute chloroquine treatment on pentylenetetrazol induced convulsions in mice. Brain research bulletin, 2016. 121: p. 124-130.
36. Kraeuter, A.-K., P.C. Guest, and Z. Sarnyai, The Y-Maze for assessment of spatial working and reference memory in mice, in Pre-Clinical Models. 2019, Springer. p. 105-111.
37. Allami, N., et al., Suppression of nitric oxide synthesis by L-NAME reverses the beneficial effects of pioglitazone on scopolamine-induced memory impairment in mice. European journal of pharmacology, 2011. 650(1): p. 240-248.
38. Javadi-Paydar, M., et al., Involvement of nitric oxide in granisetron improving effect on scopolamine-induced memory impairment in mice. Brain research, 2012. 1429: p. 61-71.
39. Karres, I., et al., Chloroquine inhibits proinflammatory cytokine release into human whole blood. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 1998. 274(4): p. R1058-R1064.
40. Malek, M.R., et al., Investigating the role of endogenous opioid system in chloroquine‐induced phospholipidosis in rat liver by morphological, biochemical and molecular modelling studies. Clinical and Experimental Pharmacology and Physiology, 2020.
41. Ajayi, A., et al., Epidemiology of antimalarial-induced pruritus in Africans. European journal of clinical pharmacology, 1989. 37(5): p. 539-540.
42. Ajayi, A., B. Kolawole, and S. Udoh, Endogenous opioids, µ‐opiate receptors and chloroquine‐induced pruritus: A double‐blind comparison of naltrexone and promethazine in patients with malaria fever who have an established history of generalized chloroquine‐induced itching. International journal of dermatology, 2004. 43(12): p. 972-977.
43. Haddadi, N.S., et al., Pharmacological evidence of involvement of nitric oxide pathway in anti‐pruritic effects of sumatriptan in chloroquine‐induced scratching in mice. Fundamental & clinical pharmacology, 2018. 32(1): p. 69-76.
44. Foroutan, A., et al., Chloroquine-induced scratching is mediated by NO/cGMP pathway in mice. Pharmacology Biochemistry and Behavior, 2015. 134: p. 79-84.
45. Nasehi, M., et al., Involvement of opioidergic and nitrergic systems in memory acquisition and exploratory behaviors in cholestatic mice. Behavioural pharmacology, 2013. 24(3): p. 180-194.
46. Haj-Mirzaian, A., et al., Resistance to depression through interference of opioid and nitrergic systems in bile-duct ligated mice. European journal of pharmacology, 2013. 708(1-3): p. 38-43.
47. Nahavandi, A., et al., The role of the interaction between endogenous opioids and nitric oxide in the pathophysiology of ethanol‐induced gastric damage in cholestatic rats. Fundamental & clinical pharmacology, 2001. 15(3): p. 181-187.
2. Prince, M.J., World Alzheimer Report 2015: the global impact of dementia: an analysis of prevalence, incidence, cost and trends. 2015: Alzheimer's Disease International.
3. Cheignon, C., et al., Oxidative stress and the amyloid beta peptide in Alzheimer’s disease. Redox biology, 2018. 14: p. 450-464.
4. Gulyaeva, N., et al., Molecular and cellular mechanisms of sporadic Alzheimer’s disease: Studies on rodent models in vivo. Biochemistry (Moscow), 2017. 82(10): p. 1088-1102.
5. Liao, Y., et al., The ameliorating effects of bee pollen on scopolamine-induced cognitive impairment in mice. Biological and Pharmaceutical Bulletin, 2019. 42(3): p. 379-388.
6. Kim, E.-J., et al., Ginsenosides Rg5 and Rh3 protect scopolamine-induced memory deficits in mice. Journal of ethnopharmacology, 2013. 146(1): p. 294-299.
7. Ishola, I.O., et al., Isorhamnetin enhanced cortico-hippocampal learning and memory capability in mice with scopolamine-induced amnesia: role of antioxidant defense, cholinergic and BDNF signaling. Brain Research, 2019. 1712: p. 188-196.
8. Rogers, S., et al., A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Neurology, 1998. 50(1): p. 136-145.
9. Doody, R.S., Refining Treatment Guidelines in Alzheimer's Disease. Geriatrics, 2005.
10. Woster, P.M., New therapies for malaria. 2003.
11. Rainsford, K., et al., Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases. Inflammopharmacology, 2015. 23(5): p. 231-269.
12. Gladman, D., Aspects of use of antimalarials in systemic lupus erythematosus. Journal of rheumatology, 1998. 25(5): p. 983-985.
13. Savarino, A., et al., Effects of chloroquine on viral infections: an old drug against today's diseases. The Lancet infectious diseases, 2003. 3(11): p. 722-727.
14. Maes, H., et al., How to teach an old dog new tricks: autophagy-independent action of chloroquine on the tumor vasculature. Autophagy, 2014. 10(11): p. 2082-2084.
15. Park, J., et al., Chloroquine induces activation of nuclear factor‐κB and subsequent expression of pro‐inflammatory cytokines by human astroglial cells. Journal of neurochemistry, 2003. 84(6): p. 1266-1274.
16. Hirata, Y., et al., Chloroquine inhibits glutamate‐induced death of a neuronal cell line by reducing reactive oxygen species through sigma‐1 receptor. Journal of neurochemistry, 2011. 119(4): p. 839-847.
17. Bartus, R.T., et al., The cholinergic hypothesis of geriatric memory dysfunction. Science, 1982. 217(4558): p. 408-414.
18. Fodale, V., et al., Alzheimer's disease and anaesthesia: implications for the central cholinergic system. BJA: British Journal of Anaesthesia, 2006. 97(4): p. 445-452.
19. Jeong, E.J., et al., Cognitive-enhancing and antioxidant activities of iridoid glycosides from Scrophularia buergeriana in scopolamine-treated mice. European journal of pharmacology, 2008. 588(1): p. 78-84.
20. Ebert, U. and W. Kirch, Scopolamine model of dementia: electroencephalogram findings and cognitive performance. European journal of clinical investigation, 1998. 28(11): p. 944.
21. Traynor, J., μ-Opioid receptors and regulators of G protein signaling (RGS) proteins: from a symposium on new concepts in mu-opioid pharmacology. Drug and alcohol dependence, 2012. 121(3): p. 173-180.
22. Liang, X., et al., Opioid system modulates the immune function: a review. Translational perioperative and pain medicine, 2016. 1(1): p. 5.
23. Onigbogi, O., A. Ajayi, and O. Ukponmwan, Mechanisms of chloroquine-induced body-scratching behavior in rats: evidence of involvement of endogenous opioid peptides. Pharmacology Biochemistry and Behavior, 2000. 65(2): p. 333-337.
24. Torres-Berrio, A. and M.O. Nava-Mesa, The opioid system in stress-induced memory disorders: From basic mechanisms to clinical implications in post-traumatic stress disorder and Alzheimer's disease. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2019. 88: p. 327-338.
25. Cai, Z. and A. Ratka, Opioid system and Alzheimer’s disease. Neuromolecular medicine, 2012. 14(2): p. 91-111.
26. Gallagher, M., Naloxone enhancement of memory processes: Effects of other opiate antagonists. Behavioral and neural biology, 1982. 35(4): p. 375-382.
27. Knowles, R.G. and S. Moncada, Nitric oxide synthases in mammals. Biochemical Journal, 1994. 298(2): p. 249-258.
28. Chen, T.-H., et al., Chloroquine induces the expression of inducible nitric oxide synthase in C6 glioma cells. Pharmacological research, 2005. 51(4): p. 329-336.
29. Böhme, G.A., et al., Possible involvement of nitric oxide in long-term potentiation. European journal of pharmacology, 1991. 199(3): p. 379-381.
30. Prada, J., et al., Upregulation of reactive oxygen and nitrogen intermediates in Plasmodium berghei infected mice after rescue therapy with chloroquine or artemether. Journal of Antimicrobial Chemotherapy, 1996. 38(1): p. 95-102.
31. Moncada, S., The 1991 Ulf von Euler Lecture: The l‐arginine: nitric oxide pathway. Acta physiologica Scandinavica, 1992. 145(3): p. 201-227.
32. Katzoff, A., T. Ben-Gedalya, and A.J. Susswein, Nitric oxide is necessary for multiple memory processes after learning that a food is inedible in Aplysia. Journal of Neuroscience, 2002. 22(21): p. 9581-9594.
33. Bannerman, D., et al., Inhibition of nitric oxide synthase does not impair spatial learning. Journal of Neuroscience, 1994. 14(12): p. 7404-7414.
34. Boultadakis, A., G. Georgiadou, and N. Pitsikas, Effects of the nitric oxide synthase inhibitor L-NAME on different memory components as assessed in the object recognition task in the rat. Behavioural brain research, 2010. 207(1): p. 208-214.
35. Hassanipour, M., et al., Possible involvement of nitrergic and opioidergic systems in the modulatory effect of acute chloroquine treatment on pentylenetetrazol induced convulsions in mice. Brain research bulletin, 2016. 121: p. 124-130.
36. Kraeuter, A.-K., P.C. Guest, and Z. Sarnyai, The Y-Maze for assessment of spatial working and reference memory in mice, in Pre-Clinical Models. 2019, Springer. p. 105-111.
37. Allami, N., et al., Suppression of nitric oxide synthesis by L-NAME reverses the beneficial effects of pioglitazone on scopolamine-induced memory impairment in mice. European journal of pharmacology, 2011. 650(1): p. 240-248.
38. Javadi-Paydar, M., et al., Involvement of nitric oxide in granisetron improving effect on scopolamine-induced memory impairment in mice. Brain research, 2012. 1429: p. 61-71.
39. Karres, I., et al., Chloroquine inhibits proinflammatory cytokine release into human whole blood. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 1998. 274(4): p. R1058-R1064.
40. Malek, M.R., et al., Investigating the role of endogenous opioid system in chloroquine‐induced phospholipidosis in rat liver by morphological, biochemical and molecular modelling studies. Clinical and Experimental Pharmacology and Physiology, 2020.
41. Ajayi, A., et al., Epidemiology of antimalarial-induced pruritus in Africans. European journal of clinical pharmacology, 1989. 37(5): p. 539-540.
42. Ajayi, A., B. Kolawole, and S. Udoh, Endogenous opioids, µ‐opiate receptors and chloroquine‐induced pruritus: A double‐blind comparison of naltrexone and promethazine in patients with malaria fever who have an established history of generalized chloroquine‐induced itching. International journal of dermatology, 2004. 43(12): p. 972-977.
43. Haddadi, N.S., et al., Pharmacological evidence of involvement of nitric oxide pathway in anti‐pruritic effects of sumatriptan in chloroquine‐induced scratching in mice. Fundamental & clinical pharmacology, 2018. 32(1): p. 69-76.
44. Foroutan, A., et al., Chloroquine-induced scratching is mediated by NO/cGMP pathway in mice. Pharmacology Biochemistry and Behavior, 2015. 134: p. 79-84.
45. Nasehi, M., et al., Involvement of opioidergic and nitrergic systems in memory acquisition and exploratory behaviors in cholestatic mice. Behavioural pharmacology, 2013. 24(3): p. 180-194.
46. Haj-Mirzaian, A., et al., Resistance to depression through interference of opioid and nitrergic systems in bile-duct ligated mice. European journal of pharmacology, 2013. 708(1-3): p. 38-43.
47. Nahavandi, A., et al., The role of the interaction between endogenous opioids and nitric oxide in the pathophysiology of ethanol‐induced gastric damage in cholestatic rats. Fundamental & clinical pharmacology, 2001. 15(3): p. 181-187.
| Files | ||
| Issue | Vol 60, No 2 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/acta.v60i2.8819 | |
| Keywords | ||
| Chloroquine Hyoscine Memory impairment Opioid receptors Nitric oxide Learning | ||
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How to Cite
1.
Mohammadi P, Karimi E, Maleki A, Rahimi N, Fakhraei N, Saadat Boroujeni S, Solaimanian S, Dehpour AR. EEffect of Chloroquine on Hyoscine-Induced Memory Impairment in Mice: Possible Involvement of Opioids and Nitric Oxide. Acta Med Iran. 2022;60(2):78-81.
