Effects Of Chronic Electroconvulsive Shock Research Articles

Activation of extracellular signal-regulated kinase signaling by chronic electroconvulsive shock in the rat frontal cortex

The effects of chronic electroconvulsive shock (ECS), given daily for 1, 5 and 10 days, on the activation of extracellular signal-regulated kinase (ERK) were studied in the rat frontal cortex. The phosphorylation of MEK1/2 and ERK1/2 increased through 5 days of ECS. Thereafter, a plateau was achieved. The expression of brain-derived neurotrophic factor was continuously increased for 10 days. Our data show that the effect of ECS on ERK1/2 signaling is increased with chronic treatment.

Functional effects of chronic electroconvulsive shock on serotonergic 5-HT 1A and 5-HT 1B receptor activity in rat hippocampus and hypothalamus

The aims of this work were to determine the influence of chronic electroconvulsive shock (ECS) on presynaptic 5-HT 1A receptor function, postsynaptic 5-HT 1A receptor function in hippocampus and hypothalamus, and presynaptic 5-HT 1B receptor function in hippocampus and hypothalamus. This represents part of an on-going study of the effects of ECS on serotonergic receptor activity in selected brain areas which may be relevant to the effects of electroconvulsive therapy (ECT) in humans. Chronic ECS reduced the ability of the 5-HT 1A receptor agonist 8-hydroxy-2(di- n-propylamino)tetraline (8-OH-DPAT) (0.2 mg/kg s.c.) to decrease 5-HT levels in hypothalamus as shown by in vivo microdialysis, indicative of a reduction in sensitivity of presynaptic 5-HT 1A autoreceptors. The ability of the 5-HT 1B receptor antagonist GR 127935 (5 mg/kg s.c.) to increase 5-HT levels in both hippocampus and hypothalamus was unaffected by chronic ECS. 8-OH-DPAT (0.2 mg/kg s.c.) increased cyclic AMP levels in hippocampus measured by in vivo microdialysis approximately 2-fold. The degree of stimulation of cyclic AMP formation was not altered by chronic ECS. However the cyclic AMP response to forskolin (50 μM) administered via the microdialysis probe, which was approximately 4-fold of basal in sham-treated rats, was almost completely abolished in ECS-treated rats. Since this indicates that either adenylate cyclase catalytic unit activity or Gs protein activity is reduced in the hippocampus after chronic ECS, the lack of change in 8-OH-DPAT-induced cyclic AMP formation may be taken as possible evidence of an increase in sensitivity of postsynaptic 5-HT 1A receptors in the hippocampus by chronic ECS. Chronic ECS increased basal plasma levels of corticosterone, ACTH and oxytocin. The ACTH response to s.c. injections of 0.2 mg/kg or 0.5 mg/kg 8-OH-DPAT was reduced by chronic ECS. Postsynaptic 5-HT 1A receptor activity in the hypothalamus, in contrast to the hippocampus, thus appears to be desensitized after chronic ECS. We conclude that chronic ECS has regionally specific effects on both pre- and post-synaptic 5-HT 1A receptors, but, in contrast to some antidepressant drugs, does not affect presynaptic 5-HT 1B receptor activity.

Effects of chronic electroconvulsive shock on the expression of beta-adrenergic receptors in rat brain: immunological study.

The purpose of the present study is to determine the effect of chronic electroconvulsive shock (ECS) on the expression of beta-adrenergic receptors in rat brain by Western blot using mAb beta CO2, a monoclonal antibody against beta-adrenergic receptors. Rats in ECS treated groups received maximal ECS (70 mA, 0.5 second, 60 Hz) through ear-clip electrodes for 12 consecutive days. The experiment was carried out in 14 discrete regions of brain. Chronic ECS reduced the expression of beta-adrenergic receptors in frontal cortex, temporal cortex, parietooccipital cortex, hippocampus and limbic forebrain, but not in other areas of brain. The regional specificity and the magnitude of the reduction of receptor expression are well correlated with those of the reduction of receptor ligand binding, which was determined using [3H]dihydroalprenolol. To the best of our knowledge, this is the first report to demonstrate that chronic ECS decreases the expression of receptor protein in specific regions of rat brain.

Molecular and Cellular Actions of Chronic Electroconvulsive Seizures

Recent studies have begun to examine the influence of electroconvulsive shock (ECS) on the expression of growth factors in brain, as well as alterations in the function and structure of certain populations of neurons. These studies demonstrate that long-term ECS increases the expression of brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, in limbic brain regions. BDNF, a member of the nerve growth-factor family, has been shown to increase the synaptic strength, survival, and growth of adult neurons. Studies in vivo and in cultured cells indicate that the induction of BDNF and TrkB is mediated by the cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB), a transcription factor that is activated by cAMP and Ca2+ intracellular pathways. Chronic ECS is also reported to induce sprouting of hippocampal neurons, and studies in BDNF mutant mice indicated that this sprouting is partially dependent on upregulation of BDNF. Increased expression of BDNF and sprouting could also contribute to the altered electrophysiologic properties of hippocampal neurons. These effects of chronic ECS are discussed with respect to recent studies demonstrating that the pathophysiology of stress and depression involves atrophy or death of hippocampal neurons. This work has led to the hypothesis that ECS and antidepressant drugs, via regulation of neurotrophic factors, reverse the atrophy of stress-vulnerable neurons or protect these neurons from further damage.

Chronic electroconvulsive shock and 5-HT autoreceptor activity in rat brain: an in vivo microdialysis study.

In vivo microdialysis was used to determine the effects of chronic electroconvulsive shock (ECS), given daily for 10 days, on basal 5-HT levels in rat frontal cortex and hippocampus and on the effect of systemic administration of the 5-HT-la receptor agonist, 8-OH-DPAT (0.2 mg/kg), to reduce 5-HT levels in these areas by activation of somatodendritic autoreceptors. Neither basal 5-HT levels nor the effects of 8-OH-DPAT on 5-HT levels were altered after chronic ECS. The effect of systemic administration of the 5-HT1A and 5-HT1B antagonist, (+/-)-pindolol (10 mg/kg), to increase 5-HT levels in hippocampus, was also not affected by chronic ECS.

In vivo cyclic AMP responses in rat brain are not modified by chronic electroconvulsive shock

In vivo microdialysis was used to determine the effects of chronic electroconvulsive shock (ECS), given daily for 10 days, on the cyclic AMP (cAMP) responses to noradrenaline (NA) and to forskolin in the cortex of freely-moving conscious rats. Microdialysis probes were inserted on the final day of ECS administration, and cAMP responses measured the following day. Chronic ECS did not modify the responses to either NA or forskolin. These results differ markedly from those previously obtained with incubated slices of rat brain. It is concluded that care is needed in interpreting results obtained by either ex vivo or in vitro methods.

Modification of effects of chronic electroconvulsive shock by voltage-dependent Ca 2+ channel blockade with nifedipine

A single electroconvulsive shock produced analgesia (expressed as prolongation of hot-plate latency) in Wistar rats 45 min after the shock. The analgesic action was prevented by administration of nifedipine, 5 mg/kg i.p., 15 min before the electroconvulsive shock, while nifedipine injection after electroconvulsive shock did not affect the analgesia significantly. At the same time single electroconvulsive shock counteracted the reduction of [ 3H]nitrendipine binding to cortical and hippocampal membranes from rats pretreated with nifedipine. Chronic administration of electroconvulsive shock (once daily for 8 days) produced hyperalgesia, augmented locomotor responses to low doses of apomorphine and upregulation of cortical (but not hippocampal) voltage-dependent Ca 2+ channels (assessed from [ 3H]nitrendipine binding). In rats receiving electroconvulsive shock chronically, always 15 min after nifedipine injection, neither behavioral hyperresponsiveness nor Ca 2+ channel upregulation was observed. The results suggest that the primary event in post-electroconvulsive shock analgesia depends on Ca 2+ influx into neurons through voltage-dependent Ca 2+ channels, and that given under conditions of Ca 2+ channel blockade electroconvulsive shock is unable to trigger changes leading to Ca 2+ channel upregulation, and this is possibly the reason for prevention of development of hyperalgesia and increased responsiveness to dopaminergic stimulation.

Effects of chronic electroconvulsive shock on interstitial concentrations of dopamine in the nucleus accumbens

There is accumulating evidence that chronic electroconvulsive shock (ECS) can increase the functional output of central dopaminergic systems. The present experiments investigated the effects of acute and chronic ECS on interstitial concentrations of dopamine (DA) in the nucleus accumbens (NAC) using in vivo microdialysis in awake freely moving rats. ECS (150 V, 0.75 s) increased interstitial concentrations of DA, DOPAC and HVA to approximately 130% of baseline values. The magnitude of the ECS-induced increase in DA was not affected by chronic ECS. In contrast, the response of the DA metabolites was attenuated in the chronic ECS group. Chronic ECS did not influence apomorphine (25 micrograms/kg, SC)-induced decreases in extracellular concentrations of DA or its metabolites in the NAC, thus providing no support for the hypothesis that chronic ECS produces subsensitivity of DA autoreceptors. d-Amphetamine (1.5 mg/kg SC)-induced increases in extracellular DA were significantly prolonged in the NAC of the chronic ECS group. In accordance with previous reports, the locomotor stimulant effects of d-amphetamine were also enhanced in the chronic ECS group. These data provide further evidence that chronic ECS can increase certain behavioral and neurochemical indices of meso-accumbens DA function.

Effects of chronic electroconvulsive shock on D 1 and D 2 dopamine receptor-mediated activity of adenylate cyclase in homogenates of striatum and limbic forebrain of rat

Stimulation of adenylate cyclase by dopamine in homogenates of the striatum was unaltered in rats which had received either a single or a series of 10 electroconvulsive shocks. However, stimulation by the selective D 1 dopamine receptor agonist SKF 38393 was significantly increased in homogenates of striatum from rats which had received chronic electroconvulsive shock, compared to those which received sham treatment. In homogenates of the limbic forebrain, stimulation by both 100 μM dopamine and by 4 μM SKF 38393 was significantly increased after chronic electroconvulsive shock. The activity of D 2 receptors, as measured by inhibition of forskolin-stimulated adenylate cyclase, in the presence of the d 1 receptor antagonist SCH 23390, was unaltered by chronic electroconvulsive shock in either area of the brain. The selective effect of chronic electroconvulsive shock in increasing the activity of D 1 receptors may account both for the increase, in dopamine-mediated behaviour, seen after chronic electroconvulsive shock and for the antiparkinsonian effects of this treatment.

Studies on the role of brain cholinergic systems in the therapeutic mechanisms and adverse effects of ECT and lithium

Brain cholinergic systems are thought to play an important role in memory function and mood regulation. Electroconvulsive therapy (ECT) and lithium (Li) have substantial therapeutic effects on abnormal mood and may adversely affect cognitive processes. The effects of chronic electroconvulsive shock (ECS) and Li administration on brain muscarinic cholinergic receptors (MCR), and on functional correlates of altered brain cholinergic activity, were therefore studied. ECS reduced MCR number in the cerebral cortex and diminished cataleptic responses to the muscarinic agonist, pilocarpine. MCR down-regulation may have therapeutic implications in depression which has been putatively linked to central cholinergic supersensitivity. Alternatively, ECS effects on brain cholinergic function may be involved in the pathogenesis of ECT-induced memory deficits. Both ECS-induced MCR subsensitivity and a clinically equivalent model of ECT-induced anterograde amnesia were not demonstrable after a single ECS, were cumulatively induced by repeated treatments, and may be reversible by administration concurrently with ECS of a muscarinic antagonist. Li increased MCR binding marginally in the cortex and hippocampus and significantly in the corpus striatum. Li substantially enhanced cataleptic and hypothermic responses to pilocarpine. Combined Li-scopolamine pretreatment had an additive effect on these cholinergically mediated responses. Effects of Li and scopolamine on MCR binding were not additive, a finding supporting the conclusion that Li enhances brain cholinergic function by its presynaptic effects on acetylcholine turnover and release. Possible implications for the therapeutic mechanisms and adverse effects of Li are considered.

Studies on the role of brain cholinergic systems in the therapeutic mechanisms and adverse effects of ECT and lithium

Brain cholinergic systems are thought to play an important role in memory function and mood regulation. Electroconvulsive therapy (ECT) and lithium (Li) have substantial therapeutic effects on abnormal mood and may adversely affect cognitive processes. The effects of chronic electroconvulsive shock (ECS) and Li administration on brain muscarinic cholinergic receptors (MCR), and on functional correlates of altered brain cholinergic activity, were therefore studied. ECS reduced MCR number in the cerebral cortex and diminished cataleptic responses to the muscarinic agonist, pilocarpine. MCR down-regulation may have therapeutic implications in depression which has been putatively linked to central cholinergic supersensitivity. Alternatively, ECS effects on brain cholinergic function may be involved in the pathogenesis of ECT-induced memory deficits. Both ECS-induced MCR subsensitivity and a clinically equivalent model of ECT-induced anterograde amnesia were not demonstrable after a single ECS, were cumulatively induced by repeated treatments, and may be reversible by administration concurrently with ECS of a muscarinic antagonist. Li increased MCR binding marginally in the cortex and hippocampus and significantly in the corpus striatum. Li substantially enhanced cataleptic and hypothermic responses to pilocarpine. Combined Li-scopolamine pretreatment had an additive effect on these cholinergically mediated responses. Effects of Li and scopolamine on MCR binding were not additive, a finding supporting the conclusion that Li enhances brain cholinergic function by its presynaptic effects on acetylcholine turnover and release. Possible implications for the therapeutic mechanisms and adverse effects of Li are considered.