JBBS  Vol.4 No.4 , April 2014
Dexamethasone Regimens Alter Spatial Memory and Anxiety Levels in Mice
Abstract: Acute and sub chronic effects of oral dexamethasone on anxiety and memory in mice were evaluated using the elevated plus maze, Y maze and radial arm maze. Adult male Swiss albino mice assigned to five groups were given vehicle (normal saline), a standard drug (Diazepam or Scopolamine) or one of three selected doses of dexamethasone (0.5, 1.0 and 1.5 mg/kg) daily for a period of 14 days. Behavioral tests were carried out on days 1 and 14 after administration. Results were analysed using a one-way ANOVA followed by a posthoc test (Student-Newman-Keul) and expressed as mean ± S.E.M. Elevated plus maze test showed a significant reduction in the time spent in the open arm and in the number of open arm entries compared to control. Results of radial arm and Y maze tasks showed an improvement in spatial memory following dexamethasone administration. Y maze locomotor activity was significantly increased, although radial arm maze exploration did not increase significantly. The study concluded that oral dexamethasone given either acutely or sub chronically has both anxiogenic and memory enhancing effects.
Cite this paper: Onaolapo, O. , Onaolapo, A. , Akinola, O. and Anisulowo, T. (2014) Dexamethasone Regimens Alter Spatial Memory and Anxiety Levels in Mice. Journal of Behavioral and Brain Science, 4, 159-167. doi: 10.4236/jbbs.2014.44019.

[1]   McEwen, B.S. (1999) Stress and Hippocampal Plasticity. Annual Review of Neuroscience, 22, 105-122.

[2]   Chrousos, G.P. and Gold, P.W. (1992) The Concepts of Stress and Stress System Disorders: Overview of Physical and Behavioral Homeostasis. Journal of the American Medical Association, 267, 1244-1252.

[3]   Ruzek, M.C., Pearce, B.D., Miller, A.H. and Biron, C.A. (1999) Endogenous Glucocorticoids Protect against Cytokine-Mediated Lethality during Viral Infection. Journal of Immunology, 162, 3527-3533.

[4]   Sandi, C.C. (2004) Stress, Cognitive Impairment and Cell Adhesion Molecules. Nature Reviews Neuroscience, 5, 917-930.

[5]   Fardet, L., Kassar, A. and Cabane, J. (2007) Corticosteroid-Induced Adverse Events in Adults: Frequency, Screening and Prevention. Drug Safety, 30, 861-881.

[6]   Herman, J.P. and Cullinan, W.E. (1997) Neurocircuitry of Stress: Central Control of the Hypothalamo-Pituitary-Adrenocortical Axis. Trends in Neuroscience, 20, 78-84.

[7]   Sandi, C. and Pinelo-Nava, M.T. (2007) Stress and Memory: Behavioral Effects and Neurobiological Mechanisms. Neural Plasticity, 2007, 78970.

[8]   Rees, L. (1953) Psychological Concomitants of Cortisone and ACTH Therapy. Journal of Mental Science, 99, 497-504.

[9]   Rome, H.P. and Braceland, F.J. (1952) The Psychological Response to ACTH, Cortisone, Hydrocortisone, and Related Steroid Substances. American Journal of Psychiatry, 108, 641-651.

[10]   Rubinow, D.R., Post, R.M., Savard, R. and Gold, P.W. (1984) Cortisol Hypersecretion and Cognitive Impairment in Depression. Archives of General Psychiatry, 41, 279-283.

[11]   McLay, R.N., Freeman, S.M. and Zadina, J.E. (1998) Chronic Corticosterone Impairs Memory Performance in the Barnes Maze. Physiology and Behavior, 63, 933-937.

[12]   Rayburn, W.F., Christensen, H.D. and Gonzalez, C.L. (1997) A Placebo-Controlled Comparison between Betamethasone and Dexamethasone for Fetal Maturation: Differences in Neurobehavioral Development of Mice Offspring. American Journal of Obstetrics & Gynecology, 176, 842-851.

[13]   Vafaei, A.A., Rashidy-Pour, A. and Taherian, A.A. (2008) Peripheral Injection of Dexamethasone Modulates Anxiety Related Behaviors. In: Mice: An Interaction with Opioidergic Neurons. Pakistan Journal of Pharmaceutical Sciences, 21, 285-289.

[14]   Onaolapo, O.J., Onaolapo, A.Y., Mosaku, T.J., Onigbinde, O.A. and Oyedele, R.A. (2012) Elevated Plus Maze and Y-Maze Behavioral Effects of Subchronic, Oral Low Dose Monosodium Glutamate in Swiss Albino Mice. IOSR Journal of Pharmacy and Biological Sciences, 3, 21-27.

[15]   Onaolapo, O.J., Onaolapo, A.Y., Awe, E.O., Jibunor, N. and Oyeleke, B. (2013) Oral Artesunate-Amodiaquine Combination Causes Anxiolysis and Impaired Cognition in Healthy Swiss Mice. IOSR Journal of Pharmacy and Biological Sciences, 7, 97-102.

[16]   Bourin, M. (1997) Animal Models of Anxiety: Are They Suitable for Predicting Drug Action in Humans? Polish Journal of Pharmacology, 49, 79-84.

[17]   File, S.E. (2001) Factors Controlling Measures of Anxiety and Responses to Novelty in the Mouse. Behavioural Brain Research, 125, 151-157.

[18]   Belzung, C. and Griebel, G. (2001) Measuring Normal and Pathological Anxiety-Like Behaviour in Mice: A Review. Behavioural Brain Research, 125, 141-149.

[19]   Handley, S.L. and Mithani, S. (1984) Effects of Adreno-receptor Agonists and Antagonists in a Maze-Exploration Model of Fear-Motivated Behaviour. Naunyn-Schmiedeberg’s Archives of Pharmacology, 327, 1-5.

[20]   Montgomery, K.C. (1958) The Relation between Fear Induced by Novel Stimulation and Exploratory Behavior. Journal of Comparative and Physiological Psychology, 48, 254-260.

[21]   Derbenev, A.V. and Smith, B.N. (2013) Dexamethasone Rapidly Increases GABA Release in the Dorsal Motor Nucleus of the Vagus via Retrograde Messenger-Mediated Enhancement of TRPV1 Activity. PLoS ONE, 8, e70505.

[22]   Wierońska, J.M., Stachowicz, K., Palucha-Poniewiera, A., Acher, F., Brański, P. and Pilc, A. (2010) Metabotropic Glutamate Receptor 4 Novel Agonist LSP1-2111 with Anxiolytic, but Not Antidepressant-Like Activity, Mediated by Serotonergic and GABAergic Systems. Neuropharmacology, 59, 627-634.

[23]   Boyle, M.P., Benedict, J.K., Vogt, K., Wozniak, D.F. and Muglia, L.J. (2006) Forebrain Glucocorticoid Receptors Modulate Anxiety-Associated Locomotor Activation and Adrenal Responsiveness. The Journal of Neuroscience, 26, 1971-1978.

[24]   Zhang, X., Kan, Q., Fu, Y., Liu, S., Dai, Z. and Dong, Y. (2012) Noradrenergic Activity Regulated Dexamethasone-Induced Increase of 5-HT3 Receptor-Mediated Glutamate Release in the Rat’s Prelimbic Cortex. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1823, 2157-2167.

[25]   Conrad, C.D. (2005) The Relationship between Acute Glucocorticoid Levels and Hippocampal Function Depends upon Task Aversiveness and Memory Processing State. Nonlinearity in Biology, Toxicology, and Medicine, 3, 57-78.

[26]   Kulkarni, S.K. (2005) Handbook of Experimental Pharmacology. 3rd Edition, Springer, Berlin, 56-66.

[27]   Sandi, C. (2011) Glucocorticoids Act on Glutamatergic Pathways to Affect Memory Processes. Trends in Neurosciences, 34.

[28]   Murph, N.P., Lam, H.A. and Maidment, N.T. (2001) A Comparison of Morphine-Induced Locomotor Activity and Mesolimbic Dopamine Release in C57BL6, 129Sv and DBA2 Mice. Journal of Neurochemistry, 79, 626-635.

[29]   Porras, G., DeDeurwaerdere, P., Moison, D. and Spampinato, U. (2003) Conditional Involvement of Striatal Serotonin3 Receptors in the Control of in Vivo Dopamine Outflow in the Rat Striatum. The European Journal of Neuroscience, 17, 771-781.