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.
[...]
Discussion
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.
