Abstract
It is recognized that chronic stress is an important risk factor for the development of several cognitive impairments involving working memory. Working memory refers to the memory in which the information to be remembered changes from trial-to-trial and should be assessed in a task able to detect retrieval of that information. In the present study, we tested the hypothesis that preventive administration of Hypericum perforatum (also named St John’s wort) may counteract the working memory impairments caused by repeated stress. Specifically, we attempted to characterize the preventive action of long-lasting treatment with St John’s wort (350 mg/kg, p.o.) on the spatial working memory impairments caused by chronic restraint stress (2 h daily for 21 days) or durable medication with exogenous corticosterone (5 mg/kg, s.c.) in male Wistar rats. Spatial working memory was tested in Barnes maze (BM) and in the Morris water maze (MWM). We found that H. perforatum prevented the deleterious effects of both chronic restraint stress and prolonged corticosterone on working memory measured in both tests. The herb significantly improved hippocampus dependent spatial working memory in comparison with control (p < 0.01) and alleviated some other negative effects of stress on cognitive functions.
Similar content being viewed by others
References
Arnsten AF (2000) Stress impairs prefrontal cortical function in rats and monkeys: role of dopamine D1 and norepinephrine alpha-1 receptor mechanism. Prog Brain Res 126:183–192
Arundine M, Tymianski M (2003) Molecular mechanisms of calcium-dependent neurodegeneration in excittotoxicity. Cell Calcium 34:325–337
Avital A, Richter-Levin G, Leschiner S, Spanier I, Veenman L, Weizman A, Gavish M (2001) Acute and repeated swim stress effects on peripheral benzodiazepine receptors in the rat hippocampus, adrenal, and kidney. Neuropsychopharmacology 25:669–678
Baker KB, Kim JJ (2002) Effects of stress and hippocampal NMDA receptor antagonism on recognition memory in rats. Learn Mem 9:58–65
Barnes CA (1979) Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat. J Comparat Physiol Psychol 1:74–104
Beck KD, Luine VN (1999) Food deprivation modulates chronic stress effects on object recognition in male rats: role monoamines and amino acids. Brain Res 830:56–71
Belanoff JK, Gross K, Yager A, Schatzberg AF (2001) Corticosteroids and cognition. J Psychiatr Res 35:127–145
Bennur S, Shankaranarayana Rao BS, Pawlak R, Strickland S, McEwen BS, Chattarji S (2007) Stress-induced spine loss in the medial amygdala is mediated by tissue-plasminogen activator. Neuroscience 144:8–16
Bowman RE, Beck KD, Luine VN (2003) Chronic stress effects on memory: sex differences in performance and monoaminergic activity. Horm Behav 43:48–59
Breyer A, Elstner M, Gillessen T, Weiser D, Elstner E (2007) Glutamate-induced cell death in neuronal HT22 cells is attenuated by extracts from St. John’s wort (Hypericum perforatum L.). Phytomedicine 14:250–255
Brezun JM, Daszuta A (2000) Serotonin may stimulate granule cell proliferation in the adult hippocampus, as observed in rats grafed with foetal raphe neurons. Eur J Neurosci 12:391–396
Butterweck V, Böckers T, Korte B, Wittkowski W, Winterhoff W (2002) Long-term effects of St. John’s wort and hypericin on monoamine levels in rat hypothalamus and hippocampus. Brain Res 930:21–29
Butterweck V, Hegger M, Winterhoff H (2004) Flavonoids of St. John’s Wort reduce HPA axis function in the rat. Planta Med 70:1008–1011
Cannon WB (1932) The wisdom of the body. Norton, New York
Chen F, Rezvani AH, Lawrence AJ (2003) Autoradiographic quantification of neurochemical markers of serotonin, dopamine and opioid systems in rat brain mesolimbic regions following chronic St. John’s wort treatment. Naunyn-Schmiedeberg’s Arch Pharmacol 367:126–133
Clinton SM, Sucharski IL, Finlay JM (2006) Desipramine attenuates working memory impairments induced by partial loss of catecholamines in the rat medial prefrontal cortex. Psychopharmacology 183:404–412
Cook SC, Wellman CL (2004) Chronic stress alters dendritic morphology in rat medial prefrontal cortex. J Neurobiol 60:236–248
ESCOP Monographs: the scientific foundation for herbal medicinal products, Second Edition (2003) Hyperici herba (St John’s wort) European Scientific Cooperative on Phytotherapy, Exeter/Stuttgart: ESCOP/Thieme Medical Publishers, 257–281
Flugge G (1995) Dynamics of central nervous 5-HT1A-receptors under psychosocial stress. J Neurosci 15:7132–7140
Galea LA, McEwen BS, Tanapat P, Deak T, Spence RL, Dhabhar FS (1997) Sex differences in dendritic atrophy of CA3 pyramidal neurons in response to chronic restraint stress. Neuroscience 81:689–697
Glenn MJ, Mumby DG (1998) Place memory is intact in rats with perirhinal cortex lesions. Behav Neurosci 112:1353–1365
Groenewegen HJ, Uylings HB (2000) The prefrontal cortex and the integration of sensory, limbic and autonomic information. Prog Brain Res 126:3–28
Herman JP, Cullinan WE (1997) Neurocircuitry of stress: central control of the hypothalamic–pituitary–adrenocortical axis. Trends Neurosci 20:78–84
Honig WK (1978) Studies of working memory in the pigeon. In: Hulse SH, Fowler H, Honig WK (eds) Cognitive processes in animal behavior. Hillsdale, NJ: Erlbaum, pp 211–248
Imperato A, Puglisi-Allegra S, Casolini P, Zocchi A, Angelluci L (1989) Stress-induced enhancement of dopamine and acetylcholine release in limbic structure: role of corticosterone. Eur J Pharmacol 165:337–339
Kehr J, Yoshitake T, Yoshitake S, Ögren SO (2002) Differential effects of acute and repeated administration of Hypericum perforatum (St. John’s wort) on extracellular levels of serotonin, noradrenaline and dopamine in prefrontal cortex, striatum and hippocampus of the rat. Eur Neuropsychopharmacol 12:203
Khalifa AE (2001) Hypericum perforatum as a nootropic drug: enhancement of retrieval memory of a passive avoidance conditioning paradigm in mice. J Etnopharmacol 76:49–57
Kim JJ, Foy MR, Thompson RF (1996) Behavioral stress modifies hippocampal plasticity trough N-methyl-D-aspartate receptor activation. Proc Natl Acad Sci USA 93:4750–4753
Kumar V, Mdzinarishvili A, Kiewert C, Abbruscato T, Bickel U, van der Schyf CJ, Klein J (2006) NMDA receptor-antagonistic properties of hyperforin, a constituent of St. John’s wort. J Pharmacol Sci 102:47–54
Lindley SE, Bengoechea TG, Schatzberg AF, Wong DL (1999) Glucocorticoids effects on mesotelencephalic dopamine neurotransmission. Neuropsychopharmacology 21:399–407
Magarinos AM, McEwen BS, Flugge G, Fuchs E (1996) Chronic psychosocial stress causes apical dendritic atrophy of hippocampal CA3 pyramidal neurons in subordinate tree shrews. J Neurosci 16:3534–3540
McEwen BS (2000) The neurobiology of stress: from serendipity to clinical relevance. Brain Res 886:172–189
Miyagawa H, Hasegawa M, Fukuta T, Amano M, Yamada K, Nabeshima T (1998) Dissociation of impairment between spatial memory, and motor function and emotional behavior in aged rats. Behav Brain Res 91:73–81
Mizoguchi K, Yuzurihara M, Ishige A, Sasaki H, Chui D-H, Tabira T (2000) Chronic stress induces impairment of spatial working memory because of prefrontal dopaminergic dysfunction. J Neurosci 15:1568–1574
Morgan CA 3rd, Doran A, Steffian G, Hazlett G, Southwick SM (2006) Stress-induced deficits in working memory and visuo-constructive abilities in Special Operations soldiers. Biol Psychiatry 60:722–729
Morris R (1984) Developments of water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 11:47–60
Murphy BL, Arnsten ATF, Goldman-Rakic PS, Roth RH (1996) Increased dopamine turnover in the prefrontal cortex impairs spatial working memory performance in rats and monkeys. Proc Natl Acad Sci USA 96:1325–1329
Neary JT, Bu Y (1999) Hypericum LI 160 inhibits uptake of serotonin and norepinephrine in astrocytes. Brain Res 816:358–363
Radley JJ, Sisti HM, Rocher AB, Hao J, McCall T, Hof PR, McEwen BS, Morrison JH (2004) Chronic behavioral stress induces apical dendritic reorganization in pyramidal neurons of the medial prefrontal cortex. Neuroscience 125:1–6
Roozendaal B, Griffith QK, Buranday J, De Quervain DJF, McGaugh JL (2003) The hippocampus mediates glucocorticoid-induced impairment of spatial memory retrieval: Dependence on the basolateral amygdala. Proc Natl Acad Sci USA 100:1328–1333
Sapolsky RM (2000) Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry 27:925–935
Sarnyai Z, Sibille EL, Pavlides C, Fenster RJ, McEwen BS, Toth M (2000) Impaired hippocampal-dependent learning and functional abnormalities in the hippocampus in mice lacking 5-HT1A receptors. Proc Natl Acad Sci USA 97:14731–14736
Schaaf MJ, De Kloet ER, Vreugdenhil E (2000) Corticosterone effects on BDNF expression in the hippocampus. Implications for memory formation. Stress 3:201–208
Shansky RM, Rubinow K, Brennan A, Arnsten AF (2006) The effects of sex and hormonal status on restraint-stress-induced working memory impairment. Behav Brain Funct 2:8
Sousa N, Lukoyanov NV, Madeira MD, Almeida OF, Paula-Barbosa MM (2000) Reorganization of the morphology of hippocampal neurites and synapses after stress-induced damage correlates with behavioral improvement. Neuroscience 97:253–266
Spencer SJ, Buller KM, Day TA (2005) Medial prefrontal cortex control of the paraventricular hypothalamic nucleus response to psychological stress: possible role of the bed nucleus of the stria terminalis. J Comp Neurol 481:363–376
Teufel-Mayer R, Gleitz J (1997) Effects of long-term administration of Hypericum extracts on the affinity and density of the central serotoninergic 5HT1A and 5HT2A receptors. Pharmacopsychiatry 30:113–116
Trofimiuk E, Walesiuk A, Braszko JJ (2005) St John’s wort (Hypericum perforatum) diminishes cognitive impairment caused by the chronic restraint stress in rats. Pharmacol Res 51:239–246
Vyas A, Mitra R, Rao BS, Chattarji S (2002) Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons. J Neurosci 2:6810–6818
Wellman C (2001) Dendritic reorganization in pyramidal neurons in medial prefrontal cortex after chronic corticosterone administration. J Neurobiol 49:245–253
Widy-Tyszkiewicz E, Piechal A, Joniec I, Blecharz-Klin K (2002) Long term administration of Hypericum perforatum improves spatial learning and memory in the water maze. Biol Pharm Bull 25:1289–94
Williams GV, Castner SA (2006) Under the curve: critical issues for elucidating D1 receptor function in working memory. Neuroscience 139(1):263–276
Acknowledgement
The study was supported by the Medical University of Bialystok (3–66 774 L).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Trofimiuk, E., Braszko, J.J. Alleviation by Hypericum perforatum of the stress-induced impairment of spatial working memory in rats. Naunyn-Schmied Arch Pharmacol 376, 463–471 (2008). https://doi.org/10.1007/s00210-007-0236-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00210-007-0236-9