Abstract
Chronic restraint stress causes spatial learning and memory deficits, dendritic atrophy of the hippocampal pyramidal neurons and alterations in the levels of neurotransmitters in the hippocampus. In contrast, intracranial self-stimulation (ICSS) rewarding behavioral experience is known to increase dendritic arborization, spine and synaptic density, and increase neurotransmitter levels in the hippocampus. In addition, ICSS facilitates operant and spatial learning, and ameliorates fornix-lesion induced behavioral deficits. Although the effects of stress and ICSS are documented, it is not known whether ICSS following stress would ameliorate the stress-induced deficits. Accordingly, the present study was aimed to evaluate the role of ICSS on stress-induced changes in hippocampal morphology, neurochemistry, and behavioral performance in the T-maze. Experiments were conducted on adult male Wistar rats, which were randomly divided into four groups; normal control, stress (ST), self-stimulation (SS), and stress + self-stimulation (ST + SS). Stress group of rats were subjected to restraint stress for 6 h daily over 21 days, SS group animals were subjected to SS from ventral tegmental area for 10 days and ST + SS rats were subjected to restraint stress for 21 days followed by 10 days of SS. Interestingly, our results show that stress-induced behavioral deficits, dendritic atrophy, and decreased levels of neurotransmitters were completely reversed following 10 days of SS experience. We propose that SS rewarding behavioral experience ameliorates the stress-induced cognitive deficits by inducing structural and biochemical changes in the hippocampus.
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Sunanda, Shankaranarayana Rao BS, Raju TR (2000) Chronic restraint stress impairs acquisition and retention of spatial memory task in rats. Curr Sci 79:1581–1584
Srikumar BN, Raju TR, Shankaranarayana Rao BS (2006) The involvement of cholinergic and noradrenergic systems in behavioral recovery following oxotremorine treatment to chronically stressed rats. Neuroscience 143:679–688
Srikumar BN, Raju TR, Shankaranarayana Rao BS (2007) Contrasting effects of bromocriptine on learning of a partially baited radial arm maze task in the presence and absence of restraint stress. Psychopharmacology (Berl) 193:363–374
Conrad CD, Galea LA, Kuroda Y et al (1996) Chronic stress impairs rat spatial memory on the Y maze, and this effect is blocked by tianeptine pretreatment. Behav Neurosci 110:1321–1334
McLay RN, Freeman SM, Zadina JE (1998) Chronic corticosterone impairs memory performance in the Barnes maze. Physiol Behav 63:933–937
Bodnoff SR, Humphreys AG, Lehman JC et al (1995) Enduring effects of chronic corticosterone treatment on spatial learning, synaptic plasticity, and hippocampal neuropathology in young and mid-aged rats. J Neurosci 15:61–69
Herbert J, Goodyer IM, Grossman AB et al (2006) Do corticosteroids damage the brain? J Neuroendocrinol 18:393–411
de Quervain DJ, Roozendaal B, McGaugh JL (1998) Stress and glucocorticoids impair retrieval of long-term spatial memory. Nature 394:787–790
Krugers HJ, Goltstein PM, van der LS et al (2006) Blockade of glucocorticoid receptors rapidly restores hippocampal CA1 synaptic plasticity after exposure to chronic stress. Eur J Neurosci 23:3051–3055
Luine VN, Spencer RL, McEwen BS (1993) Effects of chronic corticosterone ingestion on spatial memory performance and hippocampal serotonergic function. Brain Res 616:65–70
Magarinos AM, McEwen BS (1995) Stress-induced atrophy of apical dendrites of hippocampal CA3c neurons: involvement of glucocorticoid secretion and excitatory amino acid receptors. Neuroscience 69:89–98
McEwen BS (1999) Stress and hippocampal plasticity. Annu Rev Neurosci 22:105–122
Shankaranarayana Rao BS, Madhavi R, Sunanda et al (2001) Complete reversal of dendritic atrophy in CA3 neurons of the hippocampus by rehabilitation in restraint stressed rats. Curr Sci 80:653–659
Sunanda, Meti BL, Raju TR (1997) Entorhinal cortex lesioning protects hippocampal CA3 neurons from stress-induced damage. Brain Res 770:302–306
Vyas A, Mitra R, Shankaranarayana Rao BS et al (2002) Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons. J Neurosci 22:6810–6818
Sunanda, Rao MS, Raju TR (1995) Effect of chronic restraint stress on dendritic spines and excrescences of hippocampal CA3 pyramidal neurons—a quantitative study. Brain Res 694:312–317
Pawlak R, Shankaranarayana Rao BS, Melchor JP et al (2005) Tissue plasminogen activator and plasminogen mediate stress-induced decline of neuronal and cognitive functions in the mouse hippocampus. Proc Natl Acad Sci USA 102:18201–18206
Sunanda, Shankaranarayana Rao BS, Raju TR (2000) Restraint stress-induced alterations in the levels of biogenic amines, amino acids, and AChE activity in the hippocampus. Neurochem Res 25:1547–1552
Olds J (1962) Hypothalamic substrates of reward. Physiol Rev 42:554–604
Shankaranarayana Rao BS, Desiraju T, Raju TR (1993) Neuronal plasticity induced by self-stimulation rewarding experience in rats—a study on alteration in dendritic branching in pyramidal neurons of hippocampus and motor cortex. Brain Res 627:216–224
Shankaranarayana Rao BS, Desiraju T, Meti BL et al (1994) Plasticity of hippocampal and motor cortical pyramidal neurons induced by self-stimulation experience. Indian J Physiol Pharmacol 38:23–28
Shankaranarayana Rao BS, Raju TR, Meti BL (1998) Long-lasting structural changes in CA3 hippocampal and layer V motor cortical pyramidal neurons associated with self-stimulation rewarding experience: a quantitative Golgi study. Brain Res Bull 47:95–101
Shankaranarayana Rao BS, Raju TR, Meti BL (1998) Alterations in the density of excrescences in CA3 neurons of hippocampus in rats subjected to self-stimulation experience. Brain Res 804:320–324
Shankaranarayana Rao BS, Raju TR, Meti BL (1999) Increased numerical density of synapses in CA3 region of hippocampus and molecular layer of motor cortex after self-stimulation rewarding experience. Neuroscience 91:799–803
Shankaranarayana Rao BS, Raju TR, Meti BL (1999) Self-stimulation rewarding experience induced alterations in dendritic spine density in CA3 hippocampal and layer V motor cortical pyramidal neurons. Neuroscience 89:1067–1077
Shankaranarayana Rao BS, Raju TR, Meti BL (1998) Self-stimulation of lateral hypothalamus and ventral tegmentum increases the levels of noradrenaline, dopamine, glutamate, and AChE activity, but not 5-hydroxytryptamine and GABA levels in hippocampus and motor cortex. Neurochem Res 23:1053–1059
Yoganarasimha D, Shankaranarayana Rao BS, Raju TR et al (1998) Facilitation of acquisition and performance of operant and spatial learning tasks in self-stimulation experienced rats. Behav Neurosci 112:725–729
Yoganarasimha D, Meti BL (1999) Amelioration of fornix lesion induced learning deficits by self-stimulation rewarding experience. Brain Res 845:246–251
Shankaranarayana Rao BS, Raju TR (2001) Intracranial self-stimulation: an animal model to study drug addiction, depression and neuronal plasticity—a review. Proc Indian Natl Sci Acad (Biol Sci) B67:155–188
Paxinos G, Watson C (1986) The Rat Brain in Stereotaxic Coordinates. Academic Press, Sydney
Ramkumar K, Raju TR, Shankaranarayana Rao BS (2004) Intracranial self-stimulation. In: Raju TR, Kutty BM, Sathyaprabha TN et al (eds) Brain and Behavior. NIMHANS, Bangalore, pp 121–126
Shankaranarayana Rao BS, Raju TR (2004) The Golgi techniques for staining neurons. In: Raju TR, Kutty BM, Sathyaprabha TN et al (eds) Brain and Behavior. NIMHANS, Bangalore, pp 108–111
Gundappa G, Desiraju T (1988) Deviations in brain development of F2 generation on caloric undernutrition and scope of their prevention by rehabilitation: alterations in dendritic spine production and pruning of pyramidal neurons of lower laminae of motor cortex and visual cortex. Brain Res 456:205–223
Fitch JM, Juraska JM, Washington LW (1989) The dendritic morphology of pyramidal neurons in the rat hippocampal CA3 area. I. Cell types. Brain Res 479:105–114
Ellman GL, Courtney KD, Andres V Jr et al (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95
Srikumar BN, Ramkumar K, Raju TR et al (2004) Assay of acetylcholinesterase activity in the brain. In: Raju TR, Kutty BM, Sathyaprabha TN et al (eds) Brain and behavior. NIMHANS, Bangalore, pp 142–144
Deepti N, Ramkumar K, Srikumar BN et al (2004) Estimation of neurotransmitters in the brain by chromatographic methods. In: Raju TR, Kutty BM, Sathyaprabha TN et al (eds) Brain and Behavior. NIMHANS, Bangalore, pp 134–141
Srikumar BN, Bindu B, Priya V et al (2004) Methods of assessment of learning and memory in rodents. In: Raju TR, Kutty BM, Sathyaprabha TN et al (eds) Brain and Behavior. NIMHANS, Bangalore, pp 145–151
Bures J, Buresova O, Huston JP (1983) Techniques and basic experiments for the study of brain and behaviour. Elsevier Science Publishers B.V., Amsterdam
Deacon RM, Rawlins JN (2006) T-maze alternation in the rodent. Nat Protoc 1:7–12
Watanabe Y, Gould E, McEwen BS (1992) Stress induces atrophy of apical dendrites of hippocampal CA3 pyramidal neurons. Brain Res 588:341–345
Sapolsky RM, Krey LC, McEwen BS (1985) Prolonged glucocorticoid exposure reduces hippocampal neuron number: implications for aging. J Neurosci 5:1222–1227
Woolley CS, Gould E, McEwen BS (1990) Exposure to excess glucocorticoids alters dendritic morphology of adult hippocampal pyramidal neurons. Brain Res 531:225–231
Uno H, Tarara R, Else JG et al (1989) Hippocampal damage associated with prolonged and fatal stress in primates. J Neurosci 9:1705–1711
Magarinos AM, Verdugo JM, McEwen BS (1997) Chronic stress alters synaptic terminal structure in hippocampus. Proc Natl Acad Sci USA 94:14002–14008
Conrad CD, LeDoux JE, Magarinos AM et al (1999) Repeated restraint stress facilitates fear conditioning independently of causing hippocampal CA3 dendritic atrophy. Behav Neurosci 113:902–913
Amaral DG, Witter MP (1995) Hippocampal Formation. In: Paxinos G (ed) The Rat Nervous System. Academic Press, New York, NY, pp 443–493
Ibata Y, Desiraju T, Pappas GD (1971) Light and electron microscopic study of the projection of the medial septal nucleus to the hippocampus of the cat. Exp Neurol 33:103–122
Petrillo M, Ritter CA, Powers AS (1994) A role for acetylcholine in spatial memory in turtles. Physiol Behav 56:135–141
Orsetti M, Casamenti F, Pepeu G (1996) Enhanced acetylcholine release in the hippocampus and cortex during acquisition of an operant behavior. Brain Res 724:89–96
Rasmusson D, Szerb JC (1975) Cortical acetylcholine release during operant behaviour in rabbits. Life Sci 16:683–690
Anisman H (1975) Time-dependent variations in aversively motivated behaviors: nonassociative effects of cholinergic and catecholaminergic activity. Psychol Rev 82:359–385
Tizabi Y, Gilad VH, Gilad GM (1989) Effects of chronic stressors or corticosterone treatment on the septohippocampal cholinergic system of the rat. Neurosci Lett 105:177–182
Verney C, Baulac M, Berger B et al (1985) Morphological evidence for a dopaminergic terminal field in the hippocampal formation of young and adult rat. Neuroscience 14:1039–1052
Day J, Fibiger HC (1993) Dopaminergic regulation of cortical acetylcholine release: effects of dopamine receptor agonists. Neuroscience 54:643–648
Mattson MP (1988) Neurotransmitters in the regulation of neuronal cytoarchitecture. Brain Res 472:179–212
Appleyard ME (1995) Acetylcholinesterase induces long-term potentiation in CA1 pyramidal cells by a mechanism dependent on metabotropic glutamate receptors. Neurosci Lett 190:25–28
Lakshmana MK, Shankaranarayana Rao BS, Dhingra NK et al (1998) Chronic (-) deprenyl administration increases dendritic arborization in CA3 neurons of hippocampus and AChE activity in specific regions of the primate brain. Brain Res 796:38–44
Shankaranarayana Rao BS, Lakshmana MK, Meti BL et al (1999) Chronic (-) deprenyl administration alters dendritic morphology of layer III pyramidal neurons in the prefrontal cortex of adult Bonnett monkeys. Brain Res 821:218–223
Matsukawa M, Ogawa M, Nakadate K et al (1997) Serotonin and acetylcholine are crucial to maintain hippocampal synapses and memory acquisition in rats. Neurosci Lett 230:13–16
Mazer C, Muneyyirci J, Taheny K et al (1997) Serotonin depletion during synaptogenesis leads to decreased synaptic density and learning deficits in the adult rat: a possible model of neurodevelopmental disorders with cognitive deficits. Brain Res 760:68–73
Segura-Torres P, Portell-Cortes I, Morgado-Bernal I (1991) Improvement of shuttle-box avoidance with post-training intracranial self-stimulation, in rats: a parametric study. Behav Brain Res 42:161–167
Handelmann GE, Olton DS (1981) Spatial memory following damage to hippocampal CA3 pyramidal cells with kainic acid: impairment and recovery with preoperative training. Brain Res 217:41–58
Pavlides C, Watanabe Y, McEwen BS (1993) Effects of glucocorticoids on hippocampal long-term potentiation. Hippocampus 3:183–192
Gasbarri A, Sulli A, Innocenzi R et al (1996) Spatial memory impairment induced by lesion of the mesohippocampal dopaminergic system in the rat. Neuroscience 74:1037–1044
Hersi AI, Rowe W, Gaudreau P et al (1995) Dopamine D1 receptor ligands modulate cognitive performance and hippocampal acetylcholine release in memory-impaired aged rats. Neuroscience 69:1067–1074
Rosenzweig MR, Bennett EL (1996) Psychobiology of plasticity: effects of training and experience on brain and behavior. Behav Brain Res 78:57–65
George MS, Nahas Z, Borckardt JJ et al (2007) Brain stimulation for the treatment of psychiatric disorders. Curr Opin Psychiatry 20:250–254
Acknowledgments
This work was supported by research grants from Department of Science and Technology (DST), Government of India. We thank ADJ Titus for help in collating Golgi images.
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Ramkumar, K., Srikumar, B.N., Shankaranarayana Rao, B.S. et al. Self-Stimulation Rewarding Experience Restores Stress-Induced CA3 Dendritic Atrophy, Spatial Memory Deficits and Alterations in the Levels of Neurotransmitters in the Hippocampus. Neurochem Res 33, 1651–1662 (2008). https://doi.org/10.1007/s11064-007-9511-x
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DOI: https://doi.org/10.1007/s11064-007-9511-x