Implications of Cannabis sativa on serotonin receptors 1B (HTR1B) and 7 (HTR7) genes in modulation of aggression and depression

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Research Articles | Published:

Print ISSN : 0970-4078.
Online ISSN : 2229-4473.
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Pub Email: contact@vegetosindia.org
Doi: 10.1007/s42535-021-00308-9
First Page: 19
Last Page: 25
Views: 966


Keywords: Cannabis sativa , Serotonin receptors, Gene expression, Aggression, Depression


Abstract


The use of Cannabis sativa L. is rampant in the young generation and it induces diverse psychological disturbances, hence the correlation between cannabinoids and expression of serotonin receptors in modulation of depression tendencies. Alterations in the expression of serotonin receptors 1B (HTR1B) and 7 (HTR7) genes in the brain of Wistar rats after oral administration of graded doses of C. sativa extract was investigated for different durations of daily administration to establish a correlation between dose, duration of exposure and modulation of aggression/depression. C. sativa was extracted using petroleum ether as the solvent and constituents analyzed through gas chromatography. We orally administered doses of cannabis extract (12.5, 25, and 50 mg/kg) daily for 4, 8, and 12 weeks to male Wistar rats divided into 12 groups of six animals. Reverse transcriptase polymerase chain reaction (RT-PCR) technique was used to quantify the expressions of genes. Expression of HTR1B was upregulated after 4 and 8-weeks’ exposure to 50 mg/kg dose with relative expressions of 0.68 and 0.91 as compared to 0.48 and 0.52 of the control group, resulting in 41.7% and 75% upregulation. However, results got at 12 weeks revealed a downregulation in the lower doses group by 76% and 71% while the 50 mg/kg dose produced a downregulation of the gene. This suggests a reversal of effect because of prolonged exposure. The extract successfully upregulated HTR7 only after 12 weeks of exposure to 25 and 50 mg/kg doses by 22% and over 100% respectively. Cannabis sativa alters the expression of HTR1B and HTR7 and accounts for the mechanism through which users exhibit depression/aggression attributes, as well as modulation of cognitive ability.



                Cannabis sativa
              , Serotonin receptors, Gene expression, Aggression, Depression


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References


Bard JA, Zgombick J, Adham N, Vaysse P, Branchek TA, Weinshank RL. 1993. Cloning of a novel human serotonin receptor (5-HTR7) positively linked toadenylate cyclase. J Biol Chem 268 (31): 23422–23426


Batalla A, Bhattacharyya S, Yucel M, Fusar-Poli P, Crippa J, Nogue S, Torrens M, Pujol J, Farre M, Martin-Santos R (2013) Structural and functional imaging studies in chronic cannabis users: a systematic review of adolescent and adult findings. Public Libr Sci One 8(2):e55821


Berger M, Gray JA, Roth BL, Gray R (2009) The expanded biology of serotonin. Annu Rev Med 60:355–366


Brody JR, Kern SE (2004) History and principles of conductive media for standard DNA electrophoresis. Anal Biochem 333(1):1–13


Conner TS, Jensen KP, Tennen H, Furneaux HM, Kranzler HR, Covault J (2010) Functional polymorphisms in the serotonin 1B receptor gene (HTR1B) predict self-reported anger and hostility among young men. Neuropsychiatr Genet 153(1):67–78


Crabbe JC, Phillips TJ, Feller DJ (1996) Elevated alcohol consumption in null mutant mice lacking 5-HTR1B serotonin receptors. Nat Genet 14:98–101


Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G (1992) Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258:1946–1949


Dosumu O, Ugbaja R, Popoola A, Rotimi S, Owolabi O (2017) Administration of Cannabis extract causes alteration in brain and plasma nitric oxide concentration in rats. Biokemistry 29(1):56–70


Dosumu O, Taiwo O, Akinloye O, Oni E, Owolabi O, Ojo O (2020) Time-course effects of Cannabis sativa on brain Acetylcholinesterase (AChE) activity and expression of dopa decarboxylase gene (DDC). Pharmacologyonline 2:302–313


Ilan AB, Gevins A, Coleman M, ElSohly MA, de Wit H (2005) Neurophysiological and subjective profile of marijuana with varying concentrations of cannabinoids. Behav Pharmacol 16:487–496


Iversen L (2003) Cannabis and the brain. Brain 126(6):1252–1270





Malberg JE, Eisch AJ, Nestler EJ, Duman RS (2000) Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 20:9104–9110


Meier MH, Caspi A, Ambler A (2012) Persistent cannabis users show neuropsychological decline from childhood to midlife. Proc Natl Acad Sci USA 109(40):2657–2664


Mnie-Filali O, Lambás-Señas L, Zimmer L, Haddjeri N (2007) 5-HTR7 receptor antagonists as a new class of antidepressants. Drug News Perspect 20(10):613–618


Naumenko VS, Popova NK, Lacivita E, Leopoldo M, Ponimaskin EG (2014) Interplay between serotonin 5-HT1A and 5-HTR7 receptors in depressive disorders. CNS Neurosci Ther 20 (7): 582–590


Nichols DE, Nichols CD (2008) Serotonin receptors. Chem Rev 108(5):1614–1641


Pauwels PJ (1997) 5-HT 1B/1D receptor antagonists. Gen Pharmacol 29(3):293–303


Popova NK, Amstislavskaya TG (2002) Involvement of the 5-HT(1A) and 5-HT(1B) serotonergic receptor subtypes in sexual arousal in male mice. Psychoneuroendocrinology 27(5):609–618


Pytliak M, Vargová V, Mechírová V, Felšöci M (2011) Serotonin receptors—from molecular biology to clinical applications. Physiol Res Academia Scientiarum Bohemoslovaca 60(1):15–25


Ruat M, Traiffort E, Leurs R, Tardivel-Lacombe J, Diaz J, Arrang JM, Schwartz JC (1993) Molecular cloning, characterization, and localization of a high-affinity serotonin receptor (5-HTR7) activating cAMP formation. Proc Natl Acad Sci USA 90 (18): 8547–8551


Saudou F, Amara DA, Dierich A, LeMeur M, Ramboz S, Segu L (1994) Enhanced aggressive behavior in mice lacking 5-HTR1B receptor. Science 265(5180):1875–1878


Stahl SM (2010) The serotonin-7 receptor as a novel therapeutic target. J Clin Psychiatry 71(11):1414–1415


Taiwo OA, Dosumu OA, Ugbaja RN, Rotimi SO, Owolabi OP, Ojo OA (2021) Oral administration of marijuana produces alterations in 5-hydroxytryptamine receptor 3A gene (HTR3A) and electrolyte imbalances in brain of male Wistar rats. Mol Biol Res Commun 10(1):5–11. https://doi.org/10.22099/mbrc.2020.38601.1557


Tatarczynska E, Klodzinska A, Stachowicz K, Chojnacka-Wójcik E (2004) Effects of a selective 5-HTR1B receptor agonist and antagonists in animal models of anxiety and depression. Behav Pharmacol 15(8):523–534


Ugbaja R, Ademuyiwa O, Dosumu O, Onunkwo B, Faleti O, Akinhanmi T (2016) Acetylcholinesterase activity in brain regions of rats administered cannabinoids extract. Toxicol Lett 258:S195–S196


Volkow ND, Baler RD, Compton WM, Weiss SR (2014) Adverse health effects of marijuana use. N Engl J Med 370:2219–2227


Young SN (2007) How to increase serotonin in the human brain without drugs. J Psychiatry Neurosci 32(6):394–399


Zalesky A, Solowij N, Yucel M, Lubman DI, Takagi M, Harding IH (2012) Effect of long-term cannabis use on axonal fibre connectivity. Brain 135(Pt 7):2245–2255


Zhuang X, Gross C, Santarelli L, Compan V, Trillat A, Hen R (1999) Altered emotional states in knockout mice lacking 5-HT1a or 5-HTR1B receptors. Neuropsychopharmacology 21:52–60




 


Acknowledgements



Author Information


Dosumu Oluwatosin Adebisi
Department of Biochemistry, Federal University of Agriculture, Abeokuta, Nigeria

Taiwo Odunayo Anthonia
Department of Biochemistry, Federal University of Agriculture, Abeokuta, Nigeria
odunayotaiwo25@gmail.com