1. bookVolume 55 (2021): Issue 3 (July 2021)
Journal Details
License
Format
Journal
eISSN
1336-0329
First Published
30 Mar 2016
Publication timeframe
4 times per year
Languages
English
access type Open Access

Haloperidol and aripiprazole impact on the BDNF and glucocorticoid receptor levels in the rat hippocampus and prefrontal cortex: effect of the chronic mild stress

Published Online: 13 Sep 2021
Volume & Issue: Volume 55 (2021) - Issue 3 (July 2021)
Page range: 153 - 162
Journal Details
License
Format
Journal
eISSN
1336-0329
First Published
30 Mar 2016
Publication timeframe
4 times per year
Languages
English
Abstract

Objective. Changes in the brain derived neurotrophic factor (BDNF) and glucocorticoid receptor (GR) expression in the prefrontal cortex (PFC) and hippocampus (HIP) are associated with psychiatric diseases and stress response. Chronic mild stress (CMS) may alter BDNF as well as GR levels in both the PFC and the HIP. The aim of the present study was to find out whether chronic treatment with a typical antipsychotic haloperidol (HAL) and an atypical antipsychotic aripiprazole (ARI) may modify the CMS effect on the BDNF and GR expression in the above-mentioned structures.

Methods. The rats were exposed to CMS for 3 weeks and from the 7th day of CMS injected with vehicle (VEH), HAL (1 mg/kg) or ARI (10 mg/kg) for 4 weeks. BDNF and GR mRNA levels were established in the PFC and the HIP by Real Time PCR, whereas, PFC and HIP samples were obtained by punching them from 500 µm thick frozen sections. C-Fos immunoreactivity was analyzed in the PFC and the HIP on 30 µm thick paraformaldehyde fixed sections. Weight gain and corticosterone (CORT) levels were also measured.

Results. The CMS and HAL suppressed the BDNF and GR mRNA levels in the PFC. In the HIP, CMS elevated BDNF mRNA levels that were suppressed by HAL and ARI treatments. The CMS decreased the c-Fos immunoreactivity in the PFC in both HAL- and ARI-treated animals. In the HIP, HAL increased the c-Fos immunoreactivity that was again diminished in animals exposed to CMS. Stressed animals gained markedly less weight until the 7th day of CMS, however, later their weight gain did not differ from the unstressed ones or was even higher in CMS+HAL group. Un-stressed HAL and ARI animals gained less weight than the VEH ones. Neither CMS nor HAL/ARI affected the plasma CORT levels.

Conclusion. The present data indicate that HAL and ARI in the doses 1 mg/kg or 10 mg/kg, respectively, does not modify the effect of the CMS preconditioning on the BDNF and GR mRNA levels in the PFC or the HIP. However, HAL seems to modify the CMS effect on the HIP activation.

Keywords

Antoniuk S, Bijata M, Ponimaskin E, Wlodarczyk J. Chronic unpredictable mild stress for modeling depression in rodents: Meta-analysis of model reliability. Neurosci Biobehav Rev 99, 101–116, 2019.10.1016/j.neubiorev.2018.12.002 Search in Google Scholar

Ayensu WK, Pucilowski O, Mason GA, Overstreet DH, Rezvani AH, Janowsky DS. Effects of chronic mild stress on serum complement activity, saccharin preference, and corticosterone levels in Flinders lines of rats. Physiol Behav 57, 165–169, 1995.10.1016/0031-9384(94)00204-I Search in Google Scholar

Chen J, Wang ZZ, Zuo W, Zhang S, Chu SF, Chen NH. Effects of chronic mild stress on behavioral and neurobiological parameters - Role of glucocorticoid. Horm Behav 78, 150–159, 2016.10.1016/j.yhbeh.2015.11.006 Search in Google Scholar

Collins CM, Wood MD, Elliott JM. Chronic administration of haloperidol and clozapine induces differential effects on the expression of Arc and c-Fos in rat brain. J Psychopharmacol 28, 94–954, 2014.10.1177/0269881114536788 Search in Google Scholar

Dawson NM, Hamid EH, Egan MF, Meredith GE. Changes in the pattern of brain-derived neurotrophic factor immunoreactivity in the rat brain after acute and subchronic haloperidol treatment. Synapse 39, 70–81, 2001.10.1002/1098-2396(20010101)39:1<70::AID-SYN10>3.0.CO;2-J Search in Google Scholar

De Santis M, Pan B, Lian J, Huang XF, Deng C. Different effects of bifeprunox, aripiprazole, and haloperidol on body weight gain, food and water intake, and locomotor activity in rats. Pharmacol Biochem Behav 124, 167–173, 2014.10.1016/j.pbb.2014.06.004 Search in Google Scholar

Elizalde N, Garcia-Garcia AL, Totterdell S, Gendive N, Venzala E, Ramirez MJ, Del Rio J, Tordera RM. Sustained stress-induced changes in mice as a model for chronic depression. Psychopharmacology (Berl) 210, 393–406, 2010.10.1007/s00213-010-1835-6 Search in Google Scholar

Fachinetto R, Burger ME, Wagner C, Wondracek DC, Brito VB, Nogueira CW, Ferreira J, Rocha JB. High fat diet increases the incidence of orofacial dyskinesia and oxidative stress in specific brain regions of rats. Pharmacol Biochem Behav 81, 585–592, 2005.10.1016/j.pbb.2005.05.001 Search in Google Scholar

Fell MJ, Neill JC, Marshall KM. Effects of the classical antipsychotic haloperidol and atypical antipsychotic risperi-done on weight gain, the oestrous cycle and uterine weight in female rats. Eur Neuropsychopharmacol 14, 385–392, 2004.10.1016/j.euroneuro.2003.12.001 Search in Google Scholar

Froger N, Palazzo E, Boni C, Hanoun N, Saurini F, Joubert C, Dutriez-Casteloot I, Enache M, Maccari S, Barden N, Cohen-Salmon C, Hamon M, Lanfumey L. Neurochemical and behavioral alterations in glucocorticoid receptor-impaired transgenic mice after chronic mild stress. J Neurosci 24, 2787–2796, 2004. Search in Google Scholar

Godsil BP, Kiss JP, Spedding M, Jay TM. The hippocampal-prefrontal pathway: the weak link in psychiatric disorders? Eur Neuropsychopharmacol 23, 1165–1181, 2013.10.1016/j.euroneuro.2012.10.018 Search in Google Scholar

Gronli J, Bramham C, Murison R, Kanhema T, Fiske E, Bjorvatn B, Ursin R, Portas CM. Chronic mild stress inhibits BDNF protein expression and CREB activation in the dentate gyrus but not in the hippocampus proper Pharmacol Biochem Behav 85, 842–849, 2006.10.1016/j.pbb.2006.11.021 Search in Google Scholar

Hara Y, Ago Y, Taruta A, Hasebe S, Kawase H, Tanabe W, Tsukada S, Nakazawa T, Hashimoto H, Matsuda T, Takuma K. Risperidone and aripiprazole alleviate prenatal valproic acid-induced abnormalities in behaviors and dendritic spine density in mice. Psychopharmacology (Berl) 234, 3217–3228, 2017.10.1007/s00213-017-4703-9 Search in Google Scholar

Hernandez L, Hoebel BG. Haloperidol given chronically decreases basal dopamine in the prefrontal cortex more than the striatum or nucleus accumbens as simultaneously measured by microdialysis. Brain Res Bull 22, 763–769, 1989.10.1016/0361-9230(89)90097-X Search in Google Scholar

Hill MN, Hellemans KGC, Verma P, Gorzalka BB, Weinberg J. Neurobiology of chronic mild stress: parallels to major depression. Neurosci Biobehav Rev 36, 2085–2117, 2012.10.1016/j.neubiorev.2012.07.001482120122776763 Search in Google Scholar

Hudson R, Zhou Y, Leri F. The combination of escitalopram and aripiprazole: Investigation of psychomotor effects in rats. J Psychopharmacol 31, 1605–1614, 2017.10.1177/026988111773251529069975 Search in Google Scholar

Jacobson L. Hypothalamic-pituitary-adrenocortical axis: neuropsychiatric aspects. Comp Physiol 4, 715–738, 2014.10.1002/cphy.c13003624715565 Search in Google Scholar

Kompagne H, Bardos G, Szenasi G, Gacsalyi I, Harsing LG, Levay G. Chronic mild stress generates clear depressive but ambiguous anxiety-like behaviour in rats. Behav Brain Res 193, 311–314, 2008.10.1016/j.bbr.2008.06.00818590771 Search in Google Scholar

Law J, Ibarguen-Vargas Y, Belzung C, Surget A. Decline of hippocampal stress reactivity and neuronal ensemble coherence in a mouse model of depression. Psychoneuroendocrinology 67, 113–123, 2016.10.1016/j.psyneuen.2016.01.02826881837 Search in Google Scholar

Li Z, Ichikawa J, Dai J, Meltzer HY. Aripiprazole, a novel antipsychotic drug, preferentially increases dopamine release in the prefrontal cortex and hippocampus in rat brain. Eur J Pharmacol 493, 75–83, 2004.10.1016/j.ejphar.2004.04.02815189766 Search in Google Scholar

Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25, 402–408, 2001.10.1006/meth.2001.126211846609 Search in Google Scholar

Luoni A, Fumagalli F, Racagni G, Riva MA. Repeated aripiprazole treatment regulates Bdnf, Arc and Npas4 expression under basal condition as well as after an acute swim stress in the rat brain. Pharmacol Res 80, 1–8, 2014.10.1016/j.phrs.2013.11.008 Search in Google Scholar

Mao QQ, Ip SP, Ko KM, Tsai SH, Che CT. Peony glycosides produce antidepressant-like action in mice exposed to chronic unpredictable mild stress: effects on hypothalamic-pituitary-adrenal function and brain-derived neurotrophic factor. Prog Neuropsychopharmacol Biol Psychiatry 33, 1211–1216, 2009.10.1016/j.pnpbp.2009.07.002 Search in Google Scholar

Mulder R, Hamilton AH, Irwin L, Boyce P, Morris G, Porter R, Malhi G. Treating depression with adjunctive anti-psychotics. Bipolar Disord Suppl 2, 17–24, 2018.10.1111/bdi.12701 Search in Google Scholar

Musaelyan K, Yildizoglu S, Bozeman J, Du Preez A, Egeland M, Zunszain PA, Pariante CM, Fernandes C, Thuret S. Chronic stress induces significant gene expression changes in the prefrontal cortex alongside alterations in adult hippocampal neurogenesis. Brain Commun 2, fcaa153, 2020.10.1093/braincomms/fcaa153 Search in Google Scholar

Musil R, Obermeier M, Russ P, Hamerle M. Weight gain and antipsychotics: a drug safety review. Expert Opin Drug Saf 14, 73–96, 2015.10.1517/14740338.2015.974549 Search in Google Scholar

Nibuya M, Takahashi M, Russell DS, Duman RS. Repeated stress increases catalytic TrkB mRNA in rat hippocampus. Neurosci Lett 267, 81–84, 1999.10.1016/S0304-3940(99)00335-3 Search in Google Scholar

Osacka J, Szelle Cernackova A, Horvathova L, Majercikova Z, Pirnik Z, Kiss A. Clozapine impact on c-Fos expression in mild stress preconditioned male rats exposed to a novelty stressor. J Neurosci Res 96, 1786–1797, 2018.10.1002/jnr.24280 Search in Google Scholar

Pan Y, Wang FM, Qiang LQ, Zhang DM, Kong LD. Icariin attenuates chronic mild stress-induced dysregulation of the LHPA stress circuit in rats. Psychoneuroendocrinology 35, 272–283, 2010.10.1016/j.psyneuen.2009.06.020 Search in Google Scholar

Parker KJ, Schatzberg AF, Lyons DM. Neuroendocrine aspects of hypercortisolism in major depression. Horm Behav 43, 60–66, 2003.10.1016/S0018-506X(02)00016-8 Search in Google Scholar

Palkovits M, Brownstein MJ. Maps and guide to microdissection of the rat brain. New York, Elsevier, 1–223, 1988. Search in Google Scholar

Paxinos G, Watson C. The rat brain in stereotaxic coordinates. Academic Press, 2007. Search in Google Scholar

Pillai A, Mahadik SP. Differential effects of haloperidol and olanzapine on the expression of erythropoietin and its receptor in rat hippocampus and striatum. J Neurochem 98, 1411–1422, 2006.10.1111/j.1471-4159.2006.04057.x16923156 Search in Google Scholar

Pouzet B, Mow T, Kreilgaard M, Velschow S. Chronic treatment with antipsychotics in rats as a model for antipsychotic-induced weight gain in human. Pharmacol Biochem Behav 75, 133–140, 2003.10.1016/S0091-3057(03)00042-X Search in Google Scholar

Robbins MJ, Critchlow HM, Lloyd A, Cilia J, Clarke JD, Bond B, Jones DNC, Maycox PR. Differential expression of IEG mRNA in rat brain following acute treatment with clozapine or haloperidol: a semi-quantitative RTPCR study. J Psychopharmacol 22, 536–542, 2008.10.1177/0269881107081521 Search in Google Scholar

Sequeira-Cordero A, Salas-Bastos A, Fornaguera J, Brenes JC. Behavioural characterisation of chronic unpredictable stress based on ethologically relevant paradigms in rats. Sci Rep 9, 17403, 2019.10.1038/s41598-019-53624-1 Search in Google Scholar

Shen J, Li Y, Qu C, Xu L, Sun H, Zhang J. The enriched environment ameliorates chronic unpredictable mild stress-induced depressive-like behaviors and cognitive impairment by activating the SIRT1/miR-134 signaling pathway in hippocampus. J Affect Disord 248, 81–90, 2019.10.1016/j.jad.2019.01.031 Search in Google Scholar

Skrede S, Ferno J, Vazquez MJ, Fjaer S, Pavlin T, Lunder N, Vidal-Puig A, Dieguez C, Berge RK, Lopez M, Steen VM. Olanzapine, but not aripiprazole, weight-independently elevates serum triglycerides and activates lipogenic gene expression in female rats. Int J Neuropsychopharmacol 15, 163–179, 2012.10.1017/S1461145711001271 Search in Google Scholar

Song L, Che W, Min-Wei W, Murakami Y, Matsumoto K. Impairment of the spatial learning and memory induced by learned helplessness and chronic mild stress. Pharmacol Biochem Behav 83, 186–193, 2006.10.1016/j.pbb.2006.01.004 Search in Google Scholar

Sun YJ, Suzuki M, Kurachi T, Murata M, Kurachi M. Expression of Fos protein in the limbic regions of the rat following haloperidol decanoate. Brain Res 791, 125–136, 1998.10.1016/S0006-8993(98)00087-0 Search in Google Scholar

Tornese P, Sala N, Bonini D, Bonifacino T, La Via L, Milanese M, Treccani G, Seguini M, Ieraci A, Mingardi J, Nyengaard JR, Calza S, Bonanno G, Wegener G, Barbon A, Popoli M, Musazzi L. Chronic mild stress induces anhedonic behavior and changes in glutamate release, BDNF trafficking and dendrite morphology only in stress vulnerable rats. The rapid restorative action of ketamine. Neurobiol Stress 10, 100160, 2019.10.1016/j.ynstr.2019.100160 Search in Google Scholar

Tyler MW, Zaldivar-Diez J, Haggarty SJ. Classics in Chemical Neuroscience: Haloperidol. ACS Chem Neurosci 8, 444–453, 2017.10.1021/acschemneuro.7b00018 Search in Google Scholar

Westenbroek C, Den Boer JA, Ter Horst GJ. Gender-specific effects of social housing on chronic stress-induced limbic Fos expression. Neuroscience 121, 189–199, 2003.10.1016/S0306-4522(03)00367-1 Search in Google Scholar

Wiborg O. Chronic mild stress for modeling anhedonia. Cell Tissue Res 354, 155‒169, 2013.10.1007/s00441-013-1664-023801433 Search in Google Scholar

Willner P. Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacology 134, 319–329, 1997.10.1007/s0021300504569452163 Search in Google Scholar

Zhang Y, Gu F, Chen J, Dong W. Chronic antidepressant administration alleviates frontal and hippocampal BDNF deficits in CUMS rat. Brain Res 1366, 141–148, 2010.10.1016/j.brainres.2010.09.09520920483 Search in Google Scholar

Recommended articles from Trend MD

Plan your remote conference with Sciendo