mise à jour du
10 juin 2004
Europ Neuro-psychopharmacol
2004;14(6): 509-514
The effect of electroconvulsive shock seizures on behaviour induced by dopaminergic agonists and on immobility in the Porsolt test
MR Zarrindast , M Sahebgharani , W McIntyre Burnham
Department of pharmacology, school of medecine
Teheran University of medical sciences, Iran
Index de tous les travaux de MR Zarrindast


Introduction Electroconvulsive therapy (ECT) is an effective and rapid treatment for drug-resistant depression, for some types of schizophrenia and possibly, for Parkinson's disease. The mechanism of ECT's therapeutic actions, however, is still unknown.
In rats, repeated electroconvulsive shock (ECS) seizures have been found to modify the behaviour produced by pharmacological stimulation of dopaminergic, norepinephrinergic, and serotoninergic post-synaptic receptors. In particular, investigators have shown that electroshock treatment affects dopamine-mediated behaviours, such as locomotion. Drugs have been became available which selectively stimulate D-1 and D-2 dopaminergic receptors. The possibility that ECS may differentially affect the behaviours induced by activation of the D-1 and D-2 dopamine receptor subtypes has not been fully studied. Thus, in the present investigation, the effects of ECS on behaviours induced by D-1 and D-2 dopaminergic agonists were tested 1Ð2 weeks post-seizure. [...]
The present study was designed to examine the effect of repeated ECS seizures on response to dopamine agonists, and on immobility time in the Porsolt test. Dopamine receptors in the central nervous system have been classified into D-1 and D-2 receptor subtypes, with D-1 receptors being positively linked to adenylyl cyclase and D-2 receptors being negatively linked (or not linked) to adenylyl cyclase.
These two types of receptors represent distinct molecular entities, and exhibit different distributions in the brain. The present results show that the locomotor activity but not the rearing induced by the D-1/D-2 dopamine receptor agonist apomorphine is increased by repeated ECS.
However, there are results indicating that both locomotion and rearing are decreased by repeated ECS . These results are in agreement with past reports indicating that repeated ECS increases post-synaptic dopaminergic activity. Our data are in agreement with the suggestion that in ECS-induced apomorphine hyperactivity, locomotor activity is increased but stereotypies, like rearing, are not. Recent reports indicate that both D-1 and D-2 dopamine receptors are involved in dopamine-agonist mediated behaviour in rodents . The increase in apomorphine-induced locomotion, therefore, may reflect a change in either D-1 and/or D-2 receptor activation. The failure of ECS to alter rearing in the present study, suggests that different sites or receptor subtypes may mediate locomotion and rearing. ECS did not significantly alter the locomotion or rearing induced by amphetamine in the present study. These findings on locomotion are not in agreement with the reports of other authors, who have showed an increase in amphetamine-induced locomotion after repeated ECS. A "trend" toward increased locomotion was observed in the present study, but it did not reach statistical significance. Further work will be required to resolve this issue.
Grooming behaviour in rats is enhanced by D-1 agonists, such as SKF 38393. In the present study, repeated ECS significantly increased the grooming induced by SKF 38393. This suggests that repeated ECS enhances the response of post-synaptic D-1 receptors. These findings are in agreement with a previously published report indicating that repeated ECS upregulates D-1 dopamine receptors in certain areas of the rat brain. Binding sites in the striatum and nucleus accumbens were not upregulated, however, and other workers have reported that repeated ECS decreases the density of D1 dopamine receptors in the rat brain. Repeated ECS has been shown to enhance D-1 dopamine receptor turnover, which may in turn decrease the D-1 receptor density. Further work will be necessary to clarify the conflicting binding data, and their possible relation to the behavioural data obtained in the present study.
Yawning behaviour is mediated via a D-2 dopamine autoreceptor. In the present study, the D-2 and D-3 dopamine receptor agonist quinpirole induced yawning equally in control and ECS rats. These results suggest that repeated ECS did not alter the D-2 response. This finding seems consistent with the binding data which have been reported. The site of yawning induction has been shown to be in the striatum have shown that striatal D-2 binding is not changed by ECS.
Immobility in the Porsolt test is a non-drug-induced behaviour which has been linked to the dopamine system. Post-synaptic D-2 receptor stimulation has been found to decrease immobility. In the present study, immobility time was less in rats that had received repeated ECS. This is in agreement with the original report of Porsolt et al. (1978).
Our own previous datahave shown that D-2 receptor antagonists increase, while D-2 dopamine receptor agonists decrease, immobility time. The present data, therefore, may suggest that ECS induces enhanced activity in the D-2 dopaminergic system. This seems inconsistent with our findings that yawning behaviour induced by D-2 receptor activation is unchanged after ECS. It is probable, however, that two different D-2 dopamine receptor subtypes are involved in the ECS-decreased immobility time and yawning. Immobility may be related to post-synaptic D-2 receptors, or to presynaptic D-2 receptors separate from those involved in yawning.
In summary, the present data suggest that repeated ECS increases activity in D-1 and D-2 dopamine receptors. In the Porsolt test, these changes appeared to last for about 2 weeks after the last ECS trial. Further work will be required to determine the duration of the changes observed in the other tests.