Electroconvulsive Shock and Reserpine: Effects on β-Adrenergic Receptors in Rat Brain

Abstract Electroconvulsive shock (ECS) administered once daily for up to 14 days decreases β-adrenergic receptor binding in the cortex and hippocampus in a time-dependent manner. The decrease in binding in the cortex lasts at least 1 week after the last shock. In the striatum, hypothalamus, or cerebellum, 14 days of ECS did not produce significant changes in β-adrenergic receptor binding. The brain regional pattern of β-adrenergic receptor changes suggests that repeated ECS affects β-adrenergic receptors in brain regions that receive a noradrenergic innervation activated by ECS. The effects of ECS on neurotransmitter receptor binding appear to be highly selective. Of five receptors in the cortex and three receptors in the hippocampus measured, only β-adrenergic receptor binding is decreased. Chronic footshock stress does not alter β-adrenergic receptor binding sites in the cortex, indicating that the effects of ECS are not due to stress alone. The effects of ECS on reserpine-induced alterations in β-adrenergic receptor binding sites were also examined. Ten days of ECS following chronic reserpine injections reverses the increased binding of β-adrenergic receptors     

Effects of Electroconvulsive Stimuli and MK-801 on Neuropeptide Y,Neurokinin A,and Calcitonin Gene-Related Peptide in Rat Brain

Rats were pretreated with 0.9% NaCl, or 0.1 or 1.0 mg/kg MK-801, an anticonvulsant and a psychotomimetic drug, and 60 minutes later given ECS or sham ECS. After six sessions the animals were sacrificed and neuropeptide Y (NPY-), neurokinin A (NKA-), and calcitonin gene-related peptide (CGRP-) like immunoreactivity (-LI) measured with radioimmunoassays. ECS increased NPY-LI in frontal cortex, striatum, occipital cortex and hippocampus, and NKA-LI in occipital cortex and hippocampus. MK-801 increased CGRP in a dose-response manner in frontal cortex, and NKA-LI in occipital cortex. Although the higher MK-801 dose reduced seizure duration by 50%, the ECS induced NPY-LI increase in striatum, occipital cortex and hippocampus, and NKA-LI in occipital cortex was not diminished. In contrast, there was a parallel decrease in seizures and NPY-LI and NKA-LI changes in frontal cortex and hippocampus, respectively. Investigation of neuropeptides in brain may contribute to understanding of the mechanisms of action of antide-pressive and antipsychotic treatments and of psychotomimetic drugs.     

Effects of Electroconvulsive Shock on Tetrahydrobiopterin and GTP-Cyclohydrolase Activity in the Brain and Adrenal Gland of the Rat

The effects of a single and repeated electroconvulsive shock (ECS) (300 mA, 0.2 s) on tetrahydrobiopterin (BH4) levels and GTP-cyclohydrolase activity in the brain and adrenal glands of rats were examined. Twenty-four hours after the last ECS treatment (one/day for 7 days), biopterin levels were significantly elevated in the locus coeruleus, hippocampus, frontal cortex, hypothalamus, ventral tegmental area, and adrenal gland. There were no changes in biopterin levels after a single application of ECS. GTP-cyclohydrolase activity was significantly increased in the locus coeruleus, frontal cortex, hippocampus, hypothalamus, and adrenal gland 24 h after repeated ECS and remained elevated in certain tissues up to 8 days after the last treatment. Kinetic analysis of adrenal and locus coeruleus GTP-cyclohydrolase 1 day after 7 days of ECS showed significant changes in both Km and Vmax values. These data suggest that the long-term increases in BH4 levels and GTP-cyclohydrolase activity after repeated ECS may play a part in the mediation of the antidepressant effects of ECS.     

Changes in extracellular space volume and geometry induced by cortical spreading depression in immature and adult rats

Changes in extracellular space (ECS) diffusion parameters, DC potentials and extracellular potassium concentration were studied during single and repeated cortical spreading depressions (SD) in 13-15 (P13-15), 21 (P21) and 90-day-old (adult) Wistar rats. The real-time iontophoretic method using tetramethylammonium (TMA+)-selective microelectrodes was employed to measure three ECS parameters in the somatosensory cortex: the ECS volume fraction alpha (alpha = ECS volume/total tissue volume), ECS tortuosity lambda (increase in diffusion path length) and the nonspecific TMA+ uptake k'. SD was elicited by needle prick. SD was significantly longer at P13-15 than at P21 and in adults. During SD, alpha in all age groups decreased from 0.21-0.23 to 0.05-0.09; lambda increased from 1.55-1.65 to 1.95-2.07. Ten minutes after SD, alpha (in adults) and lambda (all age groups) increased compared to controls. This increase persisted even 1 hour after SD. When SD was repeated at 1 hour intervals, both alpha and lambda showed a gradual cumulative increase with SD repetition. Our study also shows that cortical SD is, as early as P13, accompanied by severe ECS shrinkage and increased diffusion path length (tortuosity) with values similar to adults, followed by a long-lasting increase in ECS volume and tortuosity when compared to pre-SD values.     

The prolonged increase in thyrotropin-releasing hormone in rat limbic forebrain regions following electroconvulsive shock

We have previously demonstrated substantial increases in thyrotropin-releasing hormone (TRH) in specific regions of rat forebrain two days after single or repeated alternate-day electroconvulsive shock (ECS). To determine longer term effects of ECS-induced seizures on forebrain TRH content, we extended the time of the post-ECS observations to 6 and 12 days following 1 (ECS x 1) or 3 (ECS x 3) alternate-day ECS. Previous observations at 2 days post-ECS were confirmed except that hippocampal content of TRH was higher after ECS x 1. In pyriform cortex TRH remained elevated for 6 days after ECS x 1 and 3, and for 12 days after ECS x 3. In hippocampus TRH was elevated for 6 days after ECS x 1 and tended to remain elevated beyond 2 days after ECS x 3. In anterior cortex the increase persisted 6 days after ECS x 1 and 12 days after ECS x 3. These data show that convulsive seizures can induce sustained elevations of TRH beyond 48 h. This finding may be especially important in pyriform cortex and hippocampus where TRH may function as an endogenous anti-epileptic. Our data are also consistent with a possible role for TRH in affective regulation in the hippocampus, amygdala, pyriform and other cortical regions. Moreover, the present results further advance the analogy of the time-course of the TRH changes in rat to the course of the antidepressant response to electroconvulsive treatment in humans.     

Diffusion properties of the brain in health and disease

Extrasynaptic transmission between neurons and communication between neurons and glia are mediated by the diffusion of neuroactive substances in the extracellular space (ECS)--volume transmission. Diffusion in the CNS is inhomogeneous and often not uniform in all directions (anisotropic). Ionic changes and amino acid release result in cellular (particularly glial) swelling, compensated for by ECS shrinkage and a decrease in the apparent diffusion coefficients of neuroactive substances or water (ADCW). The diffusion parameters of the CNS in adult mammals (including humans), ECS volume fraction alpha (alpha = ECS volume/total tissue volume; normally 0.20-0.25) and tortuosity lambda (lambda2 = D/ADC; normally 1.5-1.6), hinder the diffusion of neuroactive substances and water. A significant decrease in ECS volume and an increase in diffusion barriers (tortuosity) and anisoptropy have been observed during stimulation, lactation or learning deficits during aging, due to structural changes such as astrogliosis, the re-arrangement of astrocytic processes and a loss of extracellular matrix. Decreases in the apparent diffusion coefficient of tetramethylammonium (ADCTMA) and ADCW due to astrogliosis and increased proteoglycan expression were found in the brain after injury and in grafts of fetal tissue. Tenascin-R and tenascin C-deficient mice also showed significant changes in ADCTMA and ADCW, suggesting an important role for extracellular matrix molecules in ECS diffusion. Changes in ECS volume, tortuosity and anisotropy significantly affect neuron-glia communication, the spatial relation of glial processes towards synapses, the efficacy of glutamate or GABA 'spillover' and synaptic crosstalk, the migration of cells, the action of hormones and the toxic effects of neuroactive substances and can be important for diagnosis, drug delivery and new treatment strategies.     

Effects of frontal brain electroshock stimulation on eeg activity and memory in rats: Relationship to ECS-produced retrograde amnesia

Electroencephalographic changes occurring in rat brain following frontal cortex stimulation in non-lesioned rats and in rats with bilateral lesions in the region of amygdala were investigated in Experiment I. Seizure duration and EEG spike frequency varied systematically with current level. The amnesic effects of conventional ECS and frontal cortex stimulation were studied in Experiment II. Both treatments were highly effective in producing retrograde amnesia for an inhibitory avoidance response. The findings are interpreted as suggesting that the effectiveness of ECS in producing RA varies with the amount of current reaching the brain.     

Effect of Electroconvulsive Shock on Mitochondrial Respiratory Chain in Rat Brain

It is well described that impairment of energy production has been implicated in the pathogenesis of a number of diseases. Although several advances have occurred over the past 20 years concerning the use and administration of electroconvulsive therapy (ECT) to minimize its side effects, little progress has been made in understanding its mechanism of action. In this work, our aim was to measure the activities of mitochondrial respiratory chain complexes II and IV and succinate dehydrogenase from rat brain after acute and chronic electroconvulsive shock (ECS). Our results showed that mitochondrial respiratory chain enzymes activities were increased after acute ECS in hippocampus, striatum and cortex of rats. Besides, we also demonstrated that complex II activity was increased after chronic ECS in cortex, while hippocampus and striatum were not affected. Succinate dehydrogenase, however, was inhibited after chronic ECS in striatum, activated in cortex and not affected in hippocampus. Finally, complex IV was not affected by chronic ECS in hippocampus, striatum and cortex. Our findings demonstrated that brain metabolism is altered by ECS.     

ECS Dynamism and Its Influence on Neuronal Excitability and Seizures

Seizure activity is governed by changes in normal neuronal physiology that lead to a state of neuronal hyperexcitability and synchrony. There is a growing body of research and evidence suggesting that alterations in the volume fraction (α) of the brain’s extracellular space (ECS) have the ability to prolong or even initiate seizures. These ictogenic effects likely occur due to the ECS volume being critically important in determining both the concentration of neuroactive substances contained within it, such as ions and neurotransmitters, and the effect of electric field-mediated interactions between neurons. Changes in the size of the ECS likely both precede a seizure, assisting in its initiation, and occur during a seizure, assisting in its maintenance. Different cellular ion and water transporters and channels are essential mediators in determining neuronal excitability and synchrony and can do so through alterations in ECS volume and/or through non-ECS volume related mechanisms. This review will parse out the relationships between how the ECS volume changes during normal physiology and seizures, how those changes might alter neuronal physiology to promote seizures, and what ion and water transporters and channels are important in linking ECS volume changes and seizures.

     

Regulation of regulators of G protein signaling mRNA expression in rat brain by acute and chronic electroconvulsive seizures

G protein-coupled receptor (GPCR) signaling cascades may be key substrates for the antidepressant effects of chronic electroconvulsive seizures (ECS). To better understand changes in these signaling pathways, alterations in levels of mRNA's encoding regulators of G protein signaling (RGS) protein subtypes-2, -4, -7, -8 and -10 were evaluated in rat brain using northern blotting and in situ hybridization. In prefrontal cortex, RGS2 mRNA levels were increased several-fold 2 h following an acute ECS. Increases in RGS8 mRNA were of lesser magnitude (30%), and no changes were evident for the other RGS subtypes. At 24 h following a chronic ECS regimen, RGS4, -7, and -10 mRNA levels were reduced by 20-30%; only RGS10 was significantly reduced 24 h after acute ECS. Levels of RGS2 mRNA were unchanged 24 h following either acute or chronic ECS. In hippocampus, RGS2 mRNA levels were markedly increased 2 h following acute ECS. More modest increases were seen for RGS4 mRNA expression, whereas levels of the other RGS subtypes were unaltered. At 24 h following chronic ECS, RGS7, -8 and -10 mRNA levels were decreased in the granule cell layer, and RGS7 and -8 mRNA levels were decreased in the pyramidal cell layers. Only RGS8 and -10 mRNA levels were significantly reduced in hippocampus 24 h following an acute ECS. Paralleling neocortex, RGS2 mRNA content was unchanged in hippocampus 24 h following either acute or chronic ECS. In ventromedial hypothalamus, RGS4 mRNA content was increased 24 h following chronic ECS, whereas RGS7 mRNA levels were only increased 24 h following an acute ECS. The increased RGS4 mRNA levels in hypothalamus were significant by 2 h following an acute ECS. These studies demonstrate subtype-, time-, and region-specific regulation of RGS proteins by ECS, adaptations that may contribute to the antidepressant effects of this treatment.     

Extrasynaptic transmission and the diffusion parameters of the extracellular space

Extrasynaptic volume transmission, mediated by the diffusion of neuroactive substances in the extracellular space (ECS), plays an important role in short- and long-distance communication between nerve cells. The ability of a substance to reach extrasynaptic high-affinity receptors via diffusion depends on the ECS diffusion parameters, ECS volume fraction alpha (alpha=ECS volume/total tissue volume) and tortuosity lambda (lambda2=free/apparent diffusion coefficient), which reflects the presence of diffusion barriers represented by, e.g., fine astrocytic processes or extracellular matrix molecules. These barriers channel the migration of molecules in the ECS, so that diffusion may be facilitated in a certain direction, i.e. anisotropic. The diffusion parameters alpha and lambda differ in various brain regions, and diffusion in the CNS is therefore inhomogeneous. Changes in diffusion parameters have been found in many physiological and pathological states, such as development and aging, neuronal activity, lactation, ischemia, brain injury, degenerative diseases, tumor growth and others, in which cell swelling, glial remodeling and extracellular matrix changes are key factors influencing diffusion. Changes in ECS volume, tortuosity and anisotropy significantly affect the accumulation and diffusion of neuroactive substances and thus extrasynaptic transmission, neuron-glia communication, mediator "spillover" and synaptic crosstalk as well as, cell migration. The various changes occurring during pathological states can be important for diagnosis, drug delivery and treatment.     

Electroconvulsive Shock (ECS) and the Adenosine Neuromodulatory System: Effect of Single and Repeated ECS on the Adenosine A1 and A2 Receptors, Adenylate Cyclase, and the Adenosine Uptake Site

The effect of a single electroconvulsive shock (ECS) (30 min and 24 h after treatment) and repeated ECS (10 once-daily) on the adenosine neuromodulatory system was investigated in rat cerebral cortex, cerebellum, hippocampus, and striatum. The present study examined the adenosine A1 receptor using N6-[3H]cyclohexyladenosine ([3H]CHA), the A2 receptor using 5'-N-[3H]ethylcarboxyamidoadenosine ([ 3H]NECA), adenylate cyclase using [3H]forskolin, and the adenosine uptake site using [3H]nitrobenzylthioinosine ([3H]NBI). At 30 min after a single ECS, the Bmax of the [3H]NBI binding in striatum was increased by 20%, which is in good agreement with the well-known postictal adenosine release. The Bmax of [3H]forskolin binding in striatum and cerebellum was increased by 60 and 20%, respectively. In contrast to earlier reported changes following chemically induced seizures, [3H]CHA binding was not altered postictally. At 24 h after a single ECS, there were no changes for any ligand in any brain region. Following repeated ECS, there was a 20% increase of [3H]CHA binding sites in cerebral cortex, which lasted for at least 14 days after the last ECS. [3H]Forskolin binding in hippocampus and striatum was 20% lowered 24 h after 10 once-daily ECS but had already returned to control levels 48 h after the last treatment. Evidence is provided that the upregulated adenosine A1 receptors are coupled to guanine nucleotide binding proteins and, furthermore, that this upregulation is not paralleled by an increase in adenylate cyclase activity as labeled by [3H]forskolin.     

Glial cells and volume transmission in the CNS

Although synaptic transmission is an important means of communication between neurons, neurons themselves and neurons and glia also communicate by extrasynaptic "volume" transmission, which is mediated by diffusion in the extracellular space (ECS). The ECS of the central nervous system (CNS) is the microenvironment of neurons and glial cells. The composition and size of ECS change dynamically during neuronal activity as well as during pathological states. Following their release, a number of neuroactive substances, including ions, mediators, metabolites and neurotransmitters, diffuse via the ECS to targets distant from their release sites. Glial cells affect the composition and volume of the ECS and therefore also extracellular diffusion, particularly during development, aging and pathological states such as ischemia, injury, X-irradiation, gliosis, demyelination and often in grafted tissue. Recent studies also indicate that diffusion in the ECS is affected by ECS volume inhomogeneities, which are the result of a more compacted space in certain regions, e.g. in the vicinity of oligodendrocytes. Besides glial cells, the extracellular matrix also changes ECS geometry and forms diffusion barriers, which may also result in diffusion anisotropy. Glial cells therefore play an important role in extrasynaptic transmission, for example in functions such as vigilance, sleep, depression, chronic pain, LTP, LTD, memory formation and other plastic changes in the CNS. In turn, ECS diffusion parameters affect neuron-glia communication, ionic homeostasis and movement and/or accumulation of neuroactive substances in the brain.     

Effect of Electroconvulsive Shock on the Uptake and Release of Noradrenaline and 5-Hydroxytryptamine in Rat Brain Slices

Abstract: The uptake and release of [³H]noradrenaline and [³H]-5-hydroxytryptamine (5-HT) were studied in cerebral cortex slices from rats 30 min and 24 h after a single electroconvulsive shock (ECS) and 24 h after a series of five shocks given over 10 days. Both the K _m and V _max for 5-HT uptake were lower than controls 24 h after a single ECS, whereas after 5 ECS spread over 10 days both parameters remained depressed, though only the fall in V_max was significant. Noradrenaline uptake was not altered after a single ECS, but the V_max and K _m were elevated following chronic ECS treatment. Neither ECS treatment schedule had any effect on the potassium-stimulated release of either transmitter. It is possible that the changes in monoamine uptake seen following ECS are an adaptive response to alterations in the synaptic cleft concentration of these transmitters.     

Rat Hippocampal Lactate Efflux During Electroconvulsive Shock or Stress Is Differently Dependent on Entorhinal Cortex and Adrenal Integrity

The role of the entorhinal cortex and the adrenal gland in rat hippocampal lactate formation was assessed during and after a short-lasting immobilization stress and electroconvulsive shock (ECS). Extracellular lactate was measured on-line using microdialysis and enzyme reactions (a technique named lactography); in some rats, unilateral lesions of the entorhinal cortex were made or the bilateral adrenal glands were removed. The stress-evoked increase in hippocampus lactate was not altered either ipsi- or contralateral to an entorhinal cortex lesion. The response to ECS was attenuated only in the hippocampus ipsilateral to the entorhinal cortex lesion. Removal of bilateral adrenal glands caused some delay in the increase in hippocampal lactate after ECS and a major reduction in the stress-evoked lactate response. These results indicate that (1) the entorhinal cortex is activated by ECS, thereby activating hippocampal lactate efflux and presumably metabolism, and (2) the adrenal gland is essential in the response to stress and, to a minor extent, in the ECS-altered hippocampal metabolism.     

Amygdala Kindling Potentiates Seizure-Stimulated Immediate-Early Gene Expression in Rat Cerebral Cortex

Kindling induces long-term adaptations in neuronal function that lead to a decreased threshold for induction of seizures. In the present study, the influence of amygdala kindling on levels of mRNA for the immediate-early genes (IEGs) c-fos, c-jun, and NGF1-A were examined both before and after an acute electroconvulsive seizure (ECS). Although amygdala kindling did not significantly influence resting levels of c-fos mRNA in cerebral cortex, ECS-stimulated levels of c-fos mRNA (examined 45 min after ECS) were approximately twofold greater in the cerebral cortex of kindled rats relative to sham-treated controls. The influence of kindling on IEG expression was dependent on the time course of kindling, as ECS-stimulated levels of c-fos mRNA were not significantly increased in stage 2 kindled animals. ECS-stimulated levels of c-jun and NGF1-A mRNA were also significantly increased in cerebral cortex of kindled rats relative to sham-treated controls. The influence of kindling on IEG expression was long-lasting because an acute ECS stimulus significantly elevated levels of c-fos and c-jun mRNA in the cerebral cortex of animals that were kindled 5 months previously. In contrast to these effects in cerebral cortex, kindling did not influence ECS-stimulated levels of c-fos mRNA in hippocampus. Finally, immunohistochemical studies revealed lamina-specific changes in the cerebral cortex.(ABSTRACT TRUNCATED AT 250 WORDS)     

ALTERATIONS IN GABA METABOLISM AND MET-ENKEPHALIN CONTENT IN RAT BRAIN FOLLOWING REPEATED ELECTROCONVULSIVE SHOCKS

The effects of electroconvulsive shock (ECS; 120 V for 1 s through ear-clip electrodes) or sub-convulsive shocks (70 V for 1 s) on rat brain GABA and met-enkephalin concentration and GABA turnover has been examined 24 h after a single treatment (×1) or once daily for 10 days (×10). ECS × 10 increased GABA concentrations in the N. caudatus and N. accumbens and decreased the synthesis rate of GABA by 40% and 50% respectively in these regions. Sub-convulsive shocks (× 10 × 10) or ECS × 1 had no effect. No consistent changes were seen in the substantia nigra. Met-enkephalin concentrations increased by 50% in the N. caudatus after ECS × 10 but were unchanged in the cortex and pons/medulla. No other shock regimen had any effect on the concentration of this peptide. The results are discussed in relation to the enhanced monoamine-induced responses seen only after ECS × 10.     

In vivo regulation of the serotonin-2 receptor in rat brain

Serotonin-2 (5-HT-2) receptors in brain were measured using [3H]ketanserin. We examined the effects of amitriptyline, an antidepressant drug, of electroconvulsive shock (ECS) and of drug-induced alterations in presynaptic 5-HT function on [3H]ketanserin binding to 5-HT-2 receptors in rat brain. The importance of intact 5-HT axons to the up-regulation of 5-HT-2 receptors by ECS was also investigated, and an attempt was made to relate the ECS-induced increase in this receptor to changes in 5-HT presynaptic mechanisms. Twelve days of ECS increased the number of 5-HT-2 receptors in frontal cortex. Neither the IC50 nor the Hill coefficient of 5-HT in competing for [3H]ketanserin binding sites was altered by ECS. Repeated injections of amitriptyline reduced the number of 5-HT-2 receptors in frontal cortex. Reserpine, administered daily for 12 days, caused a significant increase in 5-HT-2 receptors, but neither daily injections of p-chlorophenylalanine (PCPA) nor lesions of 5-HT axons with 5,7-dihydroxytryptamine (5,7-DHT) affected 5-HT-2 receptors. However, regulation of 5-HT-2 receptors by ECS was dependent on intact 5-HT axons since ECS could not increase the number of 5-HT-2 receptors in rats previously lesioned with 5,7-DHT. Repeated ECS, however, does not appear to affect either the high-affinity uptake of [3H]5-HT or [3H]imipramine binding, two presynaptic markers of 5-HT neuronal function. 5-HT-2 receptors appear to be under complex control. ECS or drug treatments such as reserpine or amitriptyline, which affect several monoamine neurotransmission systems including 5-HT, can alter 5-HT-2 receptors. While depleting 5-HT alone (5,7-DHT or PCPA) does not alter [3H]ketanserin binding to 5-HT-2 receptors, intact 5-HT axons are necessary for the adaptive up-regulation of the receptor following ECS.     

Extracellular space diffusion and extrasynaptic transmission

The diffusion of neuroactive substances in the extracellular space (ECS) plays an important role in short- and long-distance communication between nerve cells and is the underlying mechanism of extrasynaptic (volume) transmission. The diffusion properties of the ECS are described by three parameters: 1. ECS volume fraction alpha (alpha=ECS volume/total tissue volume), 2. tortuosity lambda (lambda2=free/apparent diffusion coefficient), reflecting the presence of diffusion barriers represented by, e.g., fine neuronal and glial processes or extracellular matrix molecules and 3. nonspecific uptake k'. These diffusion parameters differ in various brain regions, and diffusion in the CNS is therefore inhomogeneous. Moreover, diffusion barriers may channel the migration of molecules in the ECS, so that diffusion is facilitated in a certain direction, i.e. diffusion in certain brain regions is anisotropic. Changes in the diffusion parameters have been found in many physiological and pathological states in which cell swelling, glial remodeling and extracellular matrix changes are key factors influencing diffusion. Changes in ECS volume, tortuosity and anisotropy significantly affect the accumulation and diffusion of neuroactive substances in the CNS and thus extrasynaptic transmission, neuron-glia communication, transmitter "spillover" and synaptic cross-talk as well as cell migration, drug delivery and treatment.     

Long Lasting Effects of Electroconvulsive Seizures on Brain Oxidative Parameters

This work was performed in order to determine the level of oxidative damage and antioxidant enzymes activities late after acute and chronic electroconvulsive shock (ECS) in rats. We measured oxidative parameters in hippocampus, cortex, and striatum, at 45, 60, 90 and 120 days after a single or multiple ECS. We demonstrated an increase in lipid peroxidation after multiple ECS in the hippocampus and striatum. This was also the case for protein carbonyls in the single or multiple protocols. In this way, we demonstrated an increase in catalase in cortex in contrast to striatum and hippocampus, were there were decreases sometimes in chronic ECS. The superoxide dismutase activities decrease in different times after single and multiple ECS in the hippocampus. Our findings demonstrated that there is a delayed increase after ECS in oxidative damage and decrease in antioxidant enzymes activities in hippocampus and striatum.