Chronic Electroconvulsive Shock Research Articles

Repeated ECS enhances dopamine D-1 but not D-2 agonist-induced behavioural responses in rats

The present study examined the effect of acute and repeated administration of electroconvulsive shock (ECS) on behaviours induced by various dopamine agonists in rats. Components of behavioural arousal induced by the dopamine D-1 agonist SKF 38393, the dopamine D-2 agonist RU 24213 and the mixed D-1/D-2 agonist apomorphine were assessed using a behavioural check-list method. Also, the overall behavioural syndrome produced by these drugs was measured using rating scales. Rats receiving repeated (5 times over 10 days) but not a single ECS showed enhanced grooming and sniffing in response to SKF 38393 (7.5 mg/kg) when compared to controls. Repetitive sniffing induced by apomorphine (0.5 mg/kg) was also enhanced by repeated ECS. Neither repeated nor a single ECS significantly changed behaviours induced by RU 24213 (0.75 mg/kg), although a downward trend was evident. The behaviour rating scale measurements also demonstrated that repeated administration to ECS increased behavioural responsiveness to SKF 38393 and apomorphine but not RU 24213. These results suggest that the increase of dopamine-mediated behaviour in rats seen after chronic ECS relates to an increase in central dopamine D-1 receptor function.

Chronic electroconvulsive shock treatment elicits up-regulation of CRF and AVP mRNA in select populations of neuroendocrine neurons

The effects of repeated electroconvulsive seizures (ECS) on expression of mRNAs coding for corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) in neuroendocrine neurons of the hypothalamo-pituitary-adrenocortical (HPA) axis and hypothalamo-neurohypophysial system (HNS) were assessed via semi-quantitative in situ hybridization histochemical analysis. Measures of mRNA content were accompanied by measurement of peptide- and hormone-expression in the relevant neuroendocrine systems. Following 7 daily ECS treatments, CRF mRNA was significantly increased in the medial parvocellular paraventricular nucleus (PVN) of treated rats relative to controls. CRF peptide content of whole PVN homogenates was decreased to 50% of control levels. Changes in CRF message and peptide levels were accompanied by increases in pituitary ACTH content and by elevated plasma corticosterone, suggesting ECS elicits long-term up-regulation of the HPA axis. AVP mRNA in the medial parvocellular PVN, which is known to up-regulate in response to HPA challenge by adrenalectomy, was not increased by ECS. Chronic ECS causes a clear up-regulation of HNS neurons of the supraoptic nucleus, characterized by increased AVP mRNA content, decreased AVP peptide content, and depletion of neurohypophysial AVP. However, no changes were observed in magnocellular vasopressinergic neurons of the PVN, indicating that magnocellular SON and PVN neurons respond differentially to stimulation by ECS. The data indicate that ECS is a potent stimulus for activation of select components of both the HPA axis and the HNS. As such, ECS provides a useful tool for examining mechanism underlying neuroendocrine processes.

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.

Chronic electroconvulsive shock increases D-1 receptor binding in rat substantia nigra

Chronic electroconvulsive shock increases D-1 receptor binding in rat substantia nigra

Effect of single and repeated electroconvulsive shock on the hypothalamic-pituitary-adrenal axis and plasma catecholamines in rats

The effects of single and repeated electroconvulsive shock (ECS) on the hypothalamic-pituitary-adrenal (HPA) axis and plasma catecholamines were studied. Rats were divided into three groups and each group received sham treatment, single ECS, or ten once-daily ECS. Jugular venous blood samples were obtained immediately before treatment and at 10, 30, 60, and 90 min following sham treatment, a single ECS or following the last of ten ECS. Plasma concentrations of corticosterone (CS), ACTH, immunoreactive beta-endorphin (ir-BE), epinephrine (E) and norepinephrine (NE) were determined. Following the single ECS plasma CS was significantly elevated at 10 and 30 min, ACTH was significantly elevated at 10, 30, and 60 min, whereas ir-BE and E peaked at 10 min and returned to basal concentration by 30 min. The concentration of plasma NE did not significantly vary at any time point. Following the tenth ECS the concentration of plasma CS revealed a significant attenuation of the increase at 10 and 30 min when compared with the CS changes observed following a single ECS. Plasma ACTH following chronic ECS was also significantly decreased in magnitude at 10, 30, and 60 min when compared with plasma ACTH levels following a single ECS. Ir-BE in plasma following ten ECS mirrored the changes following single ECS. In contrast to the attenuation of CS and ACTH following chronic ECS, the increase in peripheral catecholamines was markedly elevated after the last of ten ECS. Compared with single ECS, ten ECS produced significant increases in plasma E at 10, 30, and 60 min and at 10, 30, 60, and at 90 min for NE.(ABSTRACT TRUNCATED AT 250 WORDS)

Post-receptor-mediated increases in adenylate cyclase activity after chronic antidepressant treatment: relationship to receptor desensitization

Administration to rats of chronic electroconvulsive shock (ECS) or chronic desipramine (DMI, 10 mg/kg daily i.p. for 3 weeks) did not affect either basal or forskolin-stimulated adenylate cyclase activity in membranes prepared from the caudate nucleus. In cerebellar membranes prepared from rats which had received chronic ECS, forskolin-stimulated activity was significantly increased compared to activity in sham- or single ECS treated rats. Forskolin-stimulated adenylate cyclase was increased in both hippocampal and cerebellar membranes from rats which received chronic DMI, compared to saline-treated animals. In cerebellar membranes, increases comparable to those with forskolin were also obtained with guanylyl-5′-imidodiphosphate (GppNHp) after both treatments, while with Mn 2+ ions, either alone or in the additional presence of forskolin, the changes observed were similar to those previously reported in cortical membranes. A possible mechanism for these effects was investigated by studying antidepressant-induced and in vitro desensitization of the cyclic AMP response in slice preparations from the various brain areas. In slices from caudate nucleus, chronic DMI did not alter stimulation of cyclic AMP formation by either noradrenaline or forskolin, while in cerebellar slices the noradrenaline response was significantly reduced, and in hippocampal slices both responses were reduced (heterologous desensitization). In vitro incubation of cortical slices with noradrenaline also resulted in a reduction in the response to both agents. However, in membranes prepared from the desensitized cortical slices, there was no change in the degree of activation of adenylate cyclase by either NaF or forskolin. Thus, the increase in these activities observed in certain brain areas after chronic antidepressant treatment may not necessarily be related to β-adrenoceptor desensitization.

Chronic electroconvulsive shock and neurotransmitter receptors - An update -

Electroconvulsive shock (ECS) produces many neurchemical alterations which may be related to its efficacy in the treatment of different psychiatric disorders. This review focuses particularly on experimental findings of CNS receptor changes in animals following chronic ECS and relates them to neurotransmitter and behavioral changes. Also, the pharmacological effect of other anti-depressant treatment are compared. Possible mechanisms of action are discussed.

The effect of acute and chronic electroconvulsive shock on [3H]phorbol-dibutyrate binding to rat brain membranes

The present study investigated the effect of single and repeated electroconvulsive shock (ECS) on proteinkinase C in rat cerebral cortex, cerebellum, hippocampus and striatum using [3H]Phorbol-12,13-butyrate binding. In the postictal period and 24 hr after a single ECS there was no alteration in any brain region. Twenty four hr after 10 once-daily ECS there was a significant decrease the number of binding sites in cerebral cortex (30%) and in cerebellum (20%) without a change in the affinity constant. These findings are discussed with regard to earlier reports on phosphoinositide turnover following chemically and electrically induced seizures.

Chronic electroconvulsive shock and desimipramine reduce the degree of inhibition by 5-HT and carbachol of forskolin-stimulated adenylate cyclase in rat hippocampal membranes

The degree of inhibition of forskolin-stimulated adenylate cyclase activity by 5-HT and by carbachol in hippocampal membranes was significantly reduced after administration of either chronic ECS (10 days) or desimipramine (10 mg/kg i.p. for 3 weeks). A single ECS had no effect on the 5-HT response and slightly augmented the carbachol response. These results parallel previous observations on the effects of ECS and antidepressants on behavioral responses to 5-HT 1a agonists and on muscarinic receptor number, and indicate the possible involvement of these receptors in the mechanism of action of antidepressant drugs.

On the mechanism of potentiation of apomorphine-induced stereotypy due to electroconvulsive shock

Electroconvulsive shock-induced changes in the intensity of stereotypy induced by apomorphine, the binding of [ 3H]spiroperidol in the corpus striatum, the accumulation of [ 3H]dopamine in brain and the permeability of the blood-brain barrier, were monitored in rats 30 min after single, or 24 hr after chronic (once daily for 7 days) electroconvulsive shock. There was significant potentiation in stereotypy induced by apomorphine after chronic electroconvulsive shock. The binding of [ 3H]spiroperidol did not show any change in the affinity ( K d ) or density ( B max) of receptors in the striatum after acute or chronic electroconvulsive shock. The accumulation of dopamine increased significantly in the hypothalamus after acute electroconvulsive shock and in the corpus striatum and hypothalamus after chronic electroconvulsive shock. A significant increase in the entry of sodium fluorescein into the hypothalamus occurred after acute electroconvulsive shock; it increased in all the regions of the brain after chronic electroconvulsive shock. Alteration in the blood-brain barrier (BBB) by electroconvulsive shock leading to increased accumulation of dopamine in the corpus striatum may be responsible for the potentiation of stereotypy.

The effect of repeated electroconvulsive shock on GABA synthesis and release in regions of rat brain.

1 The release of endogenous gamma-aminobutyric acid (GABA) from slices of rat cortex, hippocampus and striatum prepared both 30 min and 24 h after the last of a series of electroconvulsive shocks (5 seizures given spread out over 10 days) has been investigated. 2 No change in spontaneous (basal) release was observed. However, 30 min after the last convulsion, K+-evoked GABA release above basal release was inhibited in both hippocampus (20%) and striatum (33%) but not in the cortex. Release was still inhibited in striatum (22%) 24 h after the last seizure. 3 In confirmation of an earlier report, chronic electroconvulsive shock was found to increase basal GABA content in striatum and inhibit synthesis by 34%. The synthesis rate was also inhibited in the hippocampus (44%) but not in the cortex. 4 Glutamic acid decarboxylase activity was unchanged in all regions after repeated electroconvulsive shock treatment. 5 It is proposed that repeated electroconvulsive shocks lead to a substantial inhibition of release in the striatum and hippocampus and a long-term inhibition of GABA synthesis in these regions. Such changes may be associated with the altered monoamine biochemistry and function observed after repeated electroconvulsive shock and with the mechanism of the antidepressant action of electroconvulsive therapy.

Effects of single and repeated electroconvulsive shock administration on inositol phosphate accumulation in rat brain slices.

Accumulation of inositol-1-phosphate after labeling with [3H]inositol and stimulation with noradrenaline, carbachol, and serotonin was measured in rat cortical, caudate nucleus, and hippocampal slices. The response to noradrenaline was significantly increased in cortical slices from animals that had received either a single electroconvulsive shock (ECS) or a series of 10 daily ECS but was unchanged in caudate nucleus or hippocampal slices. The response to carbachol, a muscarinic cholinergic agonist, was unchanged in cortical or caudate nucleus slices but was significantly reduced in hippocampal slices from animals that had received chronic ECS. The response to serotonin in cortical slices was not affected by the treatment. The results are correlated with changes in receptor number, which have been demonstrated to occur after administration of ECS.

Calcium antagonist binding in cat brain tolerant to electroconvulsive shock

Cats subjected to daily (25–30 days) electroconvulsive shock (ECS) demonstrated an elevation of their electroconvulsive threshold or tolerance to ECS. [ 3H] Nitrendipine binding was measured to brain regions from non-tolerant (sham shocked) and ECS tolerant cats 24 hr following the last shock. ECS produced a significant increase (45%) in the density of [ 3H] nitrendipine binding sites in the cerebral cortex and a significant decrease (33%) in the apparent affinity of [ 3H] nitrendipine in the cerebellum. No changes in binding were observed in the hippocampus. The effects of ECS were also investigated in the rat, an animal not displaying tolerance to repeated ECS. [ 3H] Nitrendipine binding to rat brain was measured 10 min and 24 hr following one shock (acute) or ten shocks delivered transauricularly once daily (chronic). Twenty-four hours following chronic ECS, there was a significant increase (19%) and decrease (11%) in the density, but no change in the apparent affinity of [ 3H] nitrendipine binding sites in the cerebral cortex and hippocampus respectively. No significant change in [ 3H] nitrendipine binding was observed in rat cerebellum 24 hr following chronic ECS. There were no changes in [ 3H] nitrendipine binding in the cerebral cortex and hippocampus 10 min and 24 hr following acute ECS. These results indicate that ECS can alter [ 3H] nitrendipine binding to calcium channel linked dihydropyridine binding sites in the central nervous system. It is suggested that changes in [ 3H] nitrendipine binding in the cat cerebellum may be involved in the development of tolerance to ECS.

Quantitative autoradiographic analysis of the effects of electroconvulsive shock on serotonin-2 receptors in male and female rats.

Chronic electroconvulsive shock (ECS) is known to increase the level of serotonin-2 (S2) receptors in male rat brain. Using quantitative autoradiography, we have studied the distribution pattern of these receptors in female as well as male rats and the effect of repeated ECS on the receptor level in both sexes. We find that although the distribution of S2 receptors is generally similar in males and females, they respond differently to repeated ECS. In males we found the expected increase in S2 binding, which was localized to specific cortical, hippocampal, and septal regions. In females, no increase was found in the cortex or septum and relatively small increases were found in the hippocampus. It appears that the regulation of S2 receptors by ECS is sex-dependent.

Opioid receptors in the brain of the rat following chronic treatment with desipramine and electroconvulsive shock

The effect of chronic administration of electroconvulsive shock and the antidepressant drug desipramine on binding to opioid receptors was studied in the cerebral cortex, the basal ganglia and the hippocampus of the forebrain of the rat. In vitro, desipramine inhibited the binding of enkephalinamide to opioid receptors through a reduction in the number of binding sites, whereas the affinity was unchanged or only slightly decreased. In vivo desipramine, injected daily (10 mg/kg) for three weeks, did not change the number of opioid binding sites in the forebrain of the rat. Chronic electroconvulsive shock, given twice a week for three weeks, had no effect on the number of opioid binding sites in the forebrain of the rat. The data do not support the hypothesis of shared effects of lithium, tricyclic antidepressants and electroconvulsive shock on the opiod peptide-opioid receptor systems.

Upregulation of brain benzodiazepine receptors by electroconvulsive shocks

Locomotor activity and footshock-induced aggressive behaviour in rat was decreased in a dose-dependant manner by diazepam. These effects were significantly potentiated by chronic electroconvulsive shock (ECS). Specific 3H-diazepam binding showed an upregulation of benzodiazepine receptors in the rat frontal cortex by ECS. This upregulation can explain the decreased therapeutic benefit observed in patients receiving both benzodiazepines and electroconvulsive shocks.

Electroconvulsive shock and cyclic AMP signal transduction: effects distal to the receptor.

Chronic electroconvulsive shock (ECS) induced a significant decrease in noradrenaline- and forskolin-stimulated cyclic AMP production in rat cortical slices, whereas a single ECS had a much smaller effect. In a cortical membrane preparation, adenylate cyclase activity in response to stimulation by forskolin, guanosine-5'-(beta,gamma-imido) triphosphate, and Mn2+ ions was significantly increased in membranes derived from rats that had received chronic ECS, but was either unchanged or reduced in membranes from rats that received a single treatment only. The results are interpreted in terms of changes occurring at components of the adenylate cyclase enzyme distal to the receptor.

Electroconvulsive shock increases endogenous monoamine oxidase inhibitor activity in brain and cerebrospinal fluid

Chronic daily administration of electroconvulsive shock (ECS) to cats resulted in a progressive elevation of seizure threshold which was accompanied by a sustained elevation in the activity of an endogenous monoamine oxidase inhibitor (EMAOI) present in cerebrospinal fluid (CSF). The increase in EMAOI activity in CSF following chronic ECS was observed maximally at 24–48 h. In rats, a single application of ECS resulted in a rapid but short-lasting increase in EMAOI activity present in the crude membrane fraction from brain. These findings demonstrate that both acute and chronic ECS modify the activity of an EMAOI in brain and CSF which may contribute to both the antidepressant and anticonvulsant effects of ECS treatment.

Endogenous asymmetry of rat brain lipids and dominance of the right cerebral hemisphere in free fatty acid response to electroconvulsive shock

An asymmetric distribution of free fatty acids (FFA) is shown to occur between right and left cerebral hemispheres (RCH, LCH) of the rat. The RCH contains 35% less FFA than the LCH, the difference being mainly accounted for by saturated and monoenoic fatty acids. Acute and chronic electroconvulsive shock (ECS) affects the distribution and apparent rate of fatty acid production differently in each hemisphere. Taking into consideration the basal content of each hemisphere, RCH produces significantly higher amounts of FFA during the acute tonic phase of the convulsion evoked by a single ECS. The largest increases correspond to arachidonic and stearic acids (1800% and 420% in RCH, 1200% and 330% in LCH, respectively). The hemispheric sidedness is evened out after successive ECSs. The removal of the released fatty acids is also faster in the RCH, as suggested by its lower FFA levels 5 min after a single shock (the acute condition) or after the last of a series of 5 daily shocks (the chronic condition). The endogenous FFA content and composition is altered by chronic ECSs. Thus, 24 h after the last of a series of 4 daily ECSs, total FFAs remain about 40% higher than in the controls for both hemispheres. Arachidonic acid increase amounts to 150%, doubling its percentage contribution to the FFA pool. The lower endogenous FFA content in RCH, its higher responsiveness to ECS, and its ability to more rapidly recover the pre-convulsive levels, suggest that the deacylation and reacylation of complex lipids are more active in this hemisphere. The results are interpreted as metabolic manifestations of brain asymmetry, possibly involving specific membrane glycerophospholipids which could in turn be related to inherently lateralized cerebral functions.

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.