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CNS & Neurological Disorders - Drug Targets


ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Review Article

An Insight through Various Models being used for Assessment of Depression and its Management at Primary Level in Current Scenario

Author(s): Rizwana Bee, Mohammad Ahmad* and Shashi Verma

Volume 22, Issue 6, 2023

Published on: 22 July, 2022

Page: [884 - 891] Pages: 8

DOI: 10.2174/1871527321666220516105907

Price: $65


Aim: The main aim of present study to assess depression and various neurotransmitters involved in it with their evaluating models.

Background: Depression is a common ailment that can be recurrent or even become chronic. According to the National Service Framework for Mental Health (released in 1999 by the Department of Health), people with depression should continue to be treated primarily in primary care settings. Despite mounting evidence that general practitioners could do a better job of detecting and treating depression, little research has been done on the perspectives of general practitioners who treat patients who are depressed. Depression (major depressive disorder) is a widespread and significant medical condition that has a negative impact on feeling, thinking, and behaviour.

Objectives: The primary goal of this study was to gather data on depression, as well as to discuss several methods for evaluating antidepressant drug response based on physical activities and neurotransmitters.

Methods: Antidepressant activity of various medications can be tested using two different types of studies, including in vivo and in vitro, according to the review.

Results: Depression is characterized by a persistent sense of sadness, insomnia, lack of concentration, slowness in activity, restlessness, social isolation and a loss of interest that prevents you from doing normal things. There are several types of depression, with symptoms ranging from mild to severe. Depression is caused by a combination of factors and conditions, rather than a single factor. Major depression is a mental condition marked by feelings of inadequacy, hopelessness, decreased activity, sadness and mood swings, which seriously disrupt and negatively affect a person's life, sometimes, leading to suicidal thoughts. The quest for a better understanding of the causes of depression and the development of more effective treatments is critical. According to clinical and preclinical research, stress appears to be a crucial mediator in the pathophysiology of depression. Using experimental models, depression may be assessed based on several physical parameters such as locomotor activity, rearing, defecation, and the number of centre square entries (in vivo and in vitro). Biological parameters may also be used to locate it.

Conclusion: Unhappiness and loss of interest in previously enjoyed activities are the symptoms of depression. It can cause emotional and physical problems, as well as a decrease in the ability to function together at work and at home. Finally it has been concluded that various neurotransmitters are involved in depression at the synaptic cleft which can be controlled using various synthetic and herbal drugs through in vitro and in vivo evaluating models.

Keywords: Depression, neurotransmitter, anhedonia, in vivo, in vitro, mental health.

Graphical Abstract
Rang H, Dale M, Ritter J, Flower R. Rang & Dale’s Pharmacology. (6th ed.). Churchill Livingstone 2007; pp. 560-80.
Maheshwari KK. Pharmacological methods and drug Screening Techniques. (1st ed.), Vallabh Prakashan 2015.
WHO. The World Health Report Mental Health. New understanding new hope. Geneva: WHO 2001.
Brigitta B. Pathophysiolosy of depression and mechanism of treatment. Dialogues Clin Neurosci 2002; 4(1): 7-20.
Baker GB, Dewhurst WG. Biochemical theories of affective disorders 1985.
Maes M, Meltzer HY. The serotonin hypothesis of major depression. Psychopharmacology; The fourth generation of progress: New York 1995; pp. 933-44.
Manji HK, Drevets WC, Charney DS. The cellular neurobiology of depression. Nat Med 2001; 7(5): 541-7.
[] [PMID: 11329053]
Sonino N, Fava GA, Raffi AR, Boscaro M, Fallo F. Clinical correlates of major depression in Cushing’s disease. Psychopathology 1998; 31(6): 302-6.
[] [PMID: 9780396]
Tripathi KD. Essentials of Medical Pharmacology. 7th ed.; India: Jaypee Brothers Medical Publishers (P) Ltd. 2013; pp. 170-462.
Hrdina PD, Demeter E, Vu TB, Sótónyi P, Palkovits M. 5-HT uptake sites and 5-HT2 receptors in brain of antidepressant-free suicide victims/depressives: Increase in 5-HT2 sites in cortex and amygdala. Brain Res 1993; 614(1-2): 37-44.
[] [PMID: 8348328]
Paul IA, Skolnick P. Glutamate and depression: Clinical and preclinical studies. Ann N Y Acad Sci 2003; 1003(1): 250-72.
[] [PMID: 14684451]
Zarate CA Jr, Du J, Quiroz J, et al. Regulation of cellular plasticity cascades in the pathophysiology and treatment of mood disorders: Role of the glutamatergic system. Ann N Y Acad Sci 2003; 1003(1): 273-91.
[] [PMID: 14684452]
Sanacora G, Gueorguieva R, Epperson CN, et al. Subtype-specific alterations of gamma-aminobutyric acid and glutamate in patients with major depression. Arch Gen Psychiatry 2004; 61(7): 705-13.
[] [PMID: 15237082]
Goodman Gilman Goodman & Gilman’s the pharmacological basis of therapeutics. (12th ed.). 2011; p. 399.
Hansen RA, Gartlehner G, Lohr KN, Gyanes BN, Carey TS. Efficacy and safety of second generation antidepressants in the treatment of major depressive disorder. Mol Psychiatry 2005; 7(1): 71-80.
Thase ME, Entsuah AR, Rudolph RL. Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors. Br J Psychiatry 2001; 178(3): 234-41.
[] [PMID: 11230034]
Moore RY, Bloom FE. Central catecholamine neuron systems: Anatomy and physiology of the dopamine systems. Annu Rev Neurosci 1978; 1(1): 129-69.
[] [PMID: 756202]
Roy A, Karoum F, Pollack S. Marked reduction in indexes of dopamine metabolism among patients with depression who attempt suicide. Arch Gen Psychiatry 1992; 49(6): 447-50.
[] [PMID: 1376107]
Reddy PL, Khanna S, Subhash MN, Channabasavanna SM, Rao BS. CSF amine metabolites in depression. Biol Psychiatry 1992; 31(2): 112-8.
[] [PMID: 1371076]
Goldberg JF, Burdick KE, Endick CJ. Preliminary randomized, double-blind, placebo-controlled trial of pramipexole added to mood stabilizers for treatment-resistant bipolar depression. Am J Psychiatry 2004; 161(3): 564-6.
[] [PMID: 14992985]
Nierenberg AA, Dougherty D, Rosenbaum JF. Dopaminergic agents and stimulants as antidepressant augmentation strategies. J Clin Psychiatry 1998; 59(5) (Suppl. 5): 60-3.
[PMID: 9635549]
Brambilla P, Perez J, Barale F, Schettini G, Soares JC. GABAergic dysfunction in mood disorders. Mol Psychiatry 2003; 8((8)): 721-737-15.
[] [PMID: 12888801]
Ku YH, Tan L, Li LS, Ding X. Role of corticotropin-releasing factor and substance P in pressor responses of nuclei controlling emotion and stress. Peptides 1998; 19(4): 677-82.
[] [PMID: 9622022]
Bittencourt JC, Benoit R, Sawchenko PE. Distribution and origins of substance P-immunoreactive projections to the paraventricular and supraoptic nuclei: Partial overlap with ascending catecholaminergic projections. J Chem Neuroanat 1991; 4(1): 63-78.
[] [PMID: 1707281]
Helke CJ, Yang L. Interactions and coexistence of neuropeptides and serotonin in spinal autonomic systems. Ann N Y Acad Sci 1996; 780(1): 185-92.
[] [PMID: 8602732]
Culman J, Unger T. Central tachykinins: Mediators of defence reaction and stress reactions. Can J Physiol Pharmacol 1995; 73(7): 885-91.
[] [PMID: 8846426]
Michel TM, Camara S, Tatschner T, et al. Increased xanthine oxidase in the thalamus and putamen in depression. World J Biol Psychiatry 2010; 11(2 Pt 2): 314-20.
[] [PMID: 20218795]
Michel TM, Frangou S, Thiemeyer D, et al. Evidence for oxidative stress in the frontal cortex in patients with recurrent depressive disorder--a postmortem study. Psychiatry Res 2007; 151(1-2): 145-50.
[] [PMID: 17296234]
Halliwell B, Gutteridge JMC. Free Radical in Biology and Medicine. Oxford: Clarendon Press 1985.
Guilloux JP, Douillard-Guilloux G, Kota R, et al. Molecular evidence for BDNF- and GABA-related dysfunctions in the amygdala of female subjects with major depression. Mol Psychiatry 2012; 17(11): 1130-42.
[] [PMID: 21912391]
Thompson DR. Motivational interviewing improves patients’ mood and reduces mortality 12 months poststroke. Evid Based Nurs 2012; 15(2): 35.
[] [PMID: 21949278]
Tripp A, Oh H, Guilloux JP, Martinowich K, Lewis DA, Sibille E. Brain-derived neurotrophic factor signaling and subgenual anterior cingulate cortex dysfunction in major depressive disorder. Am J Psychiatry 2012; 169(11): 1194-202.
[] [PMID: 23128924]
Chen B, Dowlatshahi D, MacQueen GM, Wang JF, Young LT. Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication. Biol Psychiatry 2001; 50(4): 260-5.
[] [PMID: 11522260]
Sen S, Duman R, Sanacora G. Serum brain-derived neurotrophic factor, depression, and antidepressant medications: Meta-analyses and implications. Biol Psychiatry 2008; 64(6): 527-32.
[] [PMID: 18571629]
Bocchio-Chiavetto L, Bagnardi V, Zanardini R, et al. Serum and plasma BDNF levels in major depression: A replication study and meta-analyses. World J Biol Psychiatry 2010; 11(6): 763-73.
[] [PMID: 20334574]
Dunn AJ, Swiergiel AH, de Beaurepaire R. Cytokines as mediators of depression: What can we learn from animal studies? Neurosci Biobehav Rev 2005; 29(4-5): 891-909.
[] [PMID: 15885777]
Miller AH, Maletic V, Raison CL. Inflammation and its discontents: The role of cytokines in the pathophysiology of major depression. Biol Psychiatry 2009; 65(9): 732-41.
[] [PMID: 19150053]
Yarlagadda A, Alfson E, Clayton AH. The blood brain barrier and the role of cytokines in neuropsychiatry. Psychiatry (Edgmont) 2009; 6(11): 18-22.
[PMID: 20049146]
Hannestad J, DellaGioia N, Bloch M. The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: A meta-analysis. Neuropsychopharmacology 2011; 36(12): 2452-9.
[] [PMID: 21796103]
Lewerenz J, Maher P. Chronic glutamate toxicity in neurodegenerative diseases-what is the evidence? Front Neurosci 2015; 9: 469.
[] [PMID: 26733784]
Bruhwyler J, Chleide E, Liégeois JF, Carreer F. Nitric oxide: A new messenger in the brain. Neurosci Biobehav Rev 1993; 17(4): 373-84.
[] [PMID: 7906024]
Steru L, Chermat R, Thierry B, Simon P. The tail suspension test: A new method for screening antidepressants in mice. Psychopharmacology (Berl) 1985; 85(3): 367-70.
[] [PMID: 3923523]
Maier SF, Saligman MEP. Learned helplessness. Theory and evidence. J Exp psycho 1976; 105: 3-46.
Overmier JB, Saligman MEP. Effects of inescapable shock upon subsequent escape and avoidance learning. J Comp Physiol Psychol 1967; 63: 28-33.
Christensen AB, Geoffroy M. The effect of different serotonergic drugs in the learned helplessness model of depression. Seman Scholar 1991; 1991: 205-9.
Martin P, Soubrié P, Simon P. Noradrenergic and opioid mediation of tricyclic-induced reversal of escape deficits caused by inescapable shock pretreatment in rats. Psychopharmacology (Berl) 1986; 90(1): 90-4.
[] [PMID: 3094068]
Sherman AD, Allers GL, Petty F, Henn FA. A neuropharmacologically-relevant animal model of depression. Neuropharmacology 1979; 18(11): 891-3.
[] [PMID: 575918]
Tejedor-del Real P, Glibert Rahola J, Leonsegui I, Mico JA. Relationship between emotivity level and susepsitibility to the learned helplessness model of depression in the rat. Psychol Rev 1991; 1991: 217-24.
Vogel HG. Drug discovery and evaluation pharmacological assays. (2nd ed.). New York: Spiringer 2002; p. 716.
Horovitz ZP, Ragozzino PW, Leaf RC. Selective block of rat mouse-killing by antidepressants. Life Sci 1965; 4(19): 1909-12.
[] [PMID: 5892081]
Karli P. The Norway rat’s killing response to the white mouse. An experimental analysis, behavior. JSTOR 1956; 10: 81-103.
Karli P, Vergnes M, Didiergeorges F. Rat-mouse interspecific aggressive behavior and its manipulation by brain ablation and by brain stimulation. Neuropsychopharmacology 1969; 1969: 47-55.
Hartley P, Neill D, Hagler M, Kors D, Vogel G. Procedure- and age-dependent hyperactivity in a new animal model of endogenous depression. Neurosci Biobehav Rev 1990; 14(1): 69-72.
[] [PMID: 2325942]
Mirmiran M, van de Poll NE, Corner MA, van Oyen HG, Bour HL. Suppression of active sleep by chronic treatment with chlorimipramine during early postnatal development: Effects upon adult sleep and behavior in the rat. Brain Res 1981; 204(1): 129-46.
[] [PMID: 7195762]
Dwyer SM, Rosenwasser AM. Neonatal clomipramine treatment, alcohol intake and circadian rhythms in rats. Psychopharmacology (Berl) 1998; 138(2): 176-83.
[] [PMID: 9718287]
Kinney GG, Vogel GW, Feng P. Decreased dorsal raphe nucleus neuronal activity in adult chloral hydrate anesthetized rats following neonatal clomipramine treatment: Implications for endogenous depression. Brain Res 1997; 756(1-2): 68-75.
[] [PMID: 9187315]
Neill D, Vogel G, Hagler M, Kors D, Hennessey A. Diminished sexual activity in a new animal model of endogenous depression. Neurosci Biobehav Rev 1990; 14(1): 73-6.
[] [PMID: 2325943]
Prathiba J, Kumar KB, Karanth KS. Effects of neonatal clomipramine on cholinergic receptor sensitivity and passive avoidance behavior in adult rats. J Neural Transm (Vienna) 1995; 100(2): 93-9.
[] [PMID: 8962688]
Vogel G, Neill D, Kors D, Hagler M. REM sleep abnormalities in a new animal model of endogenous depression. Neurosci Biobehav Rev 1990; 14(1): 77-83.
[] [PMID: 2325944]
Velazquez-Moctezuma J, Diaz-Ruiz O. Neonatal treatment with cloimipramine increased immobility in the forced swim test. An attribute of animal models of depression. Pharmacol Biochem Behav 1992; 42: 737-9.
Yavari P, Vogel GW, Neill DB. Decreased raphe unit activity in a rat model of endogenous depression. Brain Res 1993; 611(1): 31-6.
[] [PMID: 8390911]
Porsolt RD, Anton G, Blavet N, Jalfre M. Behavioural despair in rats: A new model sensitive to antidepressant treatments. Eur J Pharmacol 1978; 47(4): 379-91.
[] [PMID: 204499]
Porsolt RD, Bertin A, Jalfre M. Behavioural despair in mice. A primary screening test for antidepressants. Arch Int pharmacodyn 1977; 229: 327-6.
Porsolt RD, Le Pichon M, Jalfre M. Depression: A new animal model sensitive to antidepressant treatments. Nature 1977; 266(5604): 730-2.
[] [PMID: 559941]
Jancsár SM, Leonard BE. The effect of (+/-)mianserin and its enantiomers on the behavioural hyperactivity of the olfactory-bulbectomized rat. Neuropharmacology 1984; 23(9): 1065-70.
[] [PMID: 6083502]
Leonard BE, Tuite M. Anatomical, physiological, and behavioral aspects of olfactory bulbectomy in the rat. Int Rev Neurobiol 1981; 22: 251-86.
[] [PMID: 7024168]
Cairncross KD, Wren A, Cox B, Schieden H. Effects of olfactory bulbectomy and domicile on stress induced corticosteron release in the rat. Physiol Behav 1977; 19: 405-87.
Snovane GS, Sarveiya VP, Kasture VS, Kasture SB. Anxiogenic activity of Myristica fragrans seeds. Pharmacol Biochem Behav 2002; 71: 239-44.
Cuijpers P, van Straten A, Warmerdam L. Behavioral activation treatments of depression: A meta-analysis. Clin Psychol Rev 2007; 27(3): 318-26.
[] [PMID: 17184887]
Kuyken W, Byford S, Taylor RS, et al. Mindfulness-based cognitive therapy to prevent relapse in recurrent depression. J Consult Clin Psychol 2008; 76(6): 966-78.
[] [PMID: 19045965]
Mynors-Wallis LM, Gath DH, Day A, Baker F. Randomised controlled trial of problem solving treatment, antidepressant medication, and combined treatment for major depression in primary care. BMJ 2000; 320(7226): 26-30.
[] [PMID: 10617523]
ICSI. Health Care Guideline: Major Depression in Adults in Primary Care. 2009.Available from:
Hansen NB, Lambert MJ, Forman EM. The psychotherapy dose-response effect and its implications for treatment delivery services. Clin Psychol Sci Pract 2002; 9(3): 329-43.
Trivedi MH, Rush AJ, Wisniewski SR, et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: Implications for clinical practice. Am J Psychiatry 2006; 163(1): 28-40.
[] [PMID: 16390886]
Thase ME, Haight BR, Richard N, et al. Remission rates following antidepressant therapy with bupropion or selective serotonin reuptake inhibitors: A meta-analysis of original data from 7 randomized controlled trials. J Clin Psychiatry 2005; 66(8): 974-81.
[] [PMID: 16086611]

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