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Diazepam administration to mice prevents some of the changes in monoamine-mediated behaviour produced by repeated
Abstract:
Administration to mice of electroconvulsive shock (ECS) five times over 10 days results in an enhanced 5-HTP-induced head twitch response, an enhanced apomorphine-induced locomotor response and an attenuated sedation response to the alpha 2-adrenoceptor agonist clonidine. Diazepam (1.25 mg/kg IP) injected 5 min before each ECS abolished the enhanced 5-HT- and dopamine-mediated responses but left the attenuated sedation response unaltered. When diazepam was given 5 min after each convulsion it still had the same effect, although its effects on the ECS-induced changes was blocked by administration of the specific benzodiazepine antagonist Ro 15-1788 (10 mg/kg IP) at the same time as diazepam. It is concluded that diazepam can abolish the ECS-induced changes in 5-HT- and DA-mediated behaviour, but not alpha 2-adrenoceptor-mediated responses, possibly by interfering with post-ictal changes. The implications for administration of benzodiazepines during electroconvulsive therapy (ECT) are discussed.
Insights
Electroconvulsive shock (ECS) alters brain responses, but diazepam can block these changes in serotonin and dopamine pathways. However, diazepam does not affect alpha-2-adrenoceptor responses after ECS.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Electroconvulsive shock (ECS) is a model for electroconvulsive therapy (ECT).
- ECS can alter neurotransmitter systems, including serotonin (5-HT) and dopamine (DA).
- Benzodiazepines like diazepam are sometimes used during ECT, but their effects on ECS-induced neurochemical changes are not fully understood.
Purpose of the Study:
- To investigate the effects of diazepam on ECS-induced changes in neurotransmitter-mediated behaviors in mice.
- To determine if diazepam's effects are dependent on the timing of administration relative to ECS.
- To explore the role of benzodiazepine receptors in mediating these effects.
Main Methods:
- Mice received five electroconvulsive shocks (ECS) over 10 days.
- Behavioral responses to 5-HTP, apomorphine, and clonidine were measured.
- Diazepam was administered before or after ECS, with or without the benzodiazepine antagonist Ro 15-1788.
Main Results:
- ECS enhanced 5-HTP-induced head twitches and apomorphine-induced locomotion.
- ECS attenuated sedation induced by clonidine (an alpha-2-adrenoceptor agonist).
- Diazepam administered before or after ECS abolished the enhanced 5-HT and dopamine responses but not the attenuated alpha-2-adrenoceptor response.
Conclusions:
- Diazepam can reverse ECS-induced alterations in serotonin and dopamine pathways.
- Diazepam does not affect ECS-induced changes in alpha-2-adrenoceptor-mediated responses.
- These findings suggest diazepam may interfere with post-ictal changes, with implications for benzodiazepine use during ECT.